Experimental Investigations on The Effects Of Paroxetine in Somatic

Sensitivity in Mice

Author: Martha Gismondi

Co-authors: Ludovica Corsello, Rosaria Tartarone
Scientific Coordinator: Associate Professor Liliana Mititelu-Taru, MD, PhD

Introduction: Paroxetine, a phenylpiperidine derivative, is the most potent inhibitor

of the reuptake of serotonin of all currently available antidepressants including the
class of SSRIs, which has neuro-modulatory and analgesic properties independent of
its psychotropic effect. It potently and selectively inhibits neuronal serotonin reuptake
through antagonism of the serotonin transporter. Experimental researches on the
effects of paroxetine in a somatic pain model in mice.

Material and Methods: The experiment was carried out with white Swiss mice (20-
25g) divided into 4 groups of 7 animals each, treated orally (using an eso-gastric
device), with the same volume of solution (0,3ml) for 7 days, as follows: Group I
(DW): distilled water 0,1 ml/10 g body weight; Group II (PRX-1): paroxetine 1
mg/kbw; Group III (PRX-3): paroxetine 3 mg/kbw; Group IV (MTZ): metamizole 10
mg/kbw. Hot plate was used to assess paroxetine-induced antinociception. The
latency to first sign of hind paw licking or jump response to avoid heat nociception
was taken as an index of nociceptive threshold. The values corresponding for every
time period were statistically processed using SPSS for Windows version 13.0 and
ANOVA method. The experiment was performed according to the guidelines of the
``Grigore T. Popa`` University of Medicine and Pharmacy.

Results: Paroxetine (3 mg/kbw) prolonged the latency time response statistically

significant (p<0,05) comparing with control group, 15 minutes after painful thermal
stimulus application. Its effects were less intense than those of metamizole, the
positive control substance with known antinociceptive activity in hot plate test in
mice.

Conclusion: administration of 3 mg/kbw paroxetine determined analgesic effects in

hot plate in mice.

Keywords: Paroxetine, Hot-plate, Nociception

CAR T Cells: A Novel Approach in Cancer Immunotherapy

Author: Maria Antoanela Pasare

Scientific Coordinator: Professor Petru Cianga, MD, PhD

Introduction: The continuous increase of cancer incidence exerts a

strong pressure to discover and test safer and more specific treatments.
Chimeric antigen receptor T-cells (CARs) are a new form of immunotherapy based on
engineering T-cells. CARs link a single chain variable fragment derived from
antibodies with different intracellular signaling and stimulatory domains that activate
the T lymphocytes. CARs are thus able to recognize specific tumor cells in a MHC-
independent manner.

Material and Methods: We have used the Google Scholar and PubMed search
engines to perform a literature analysis targeting CARs. As a result, we were able to
identify 20 clinical trials that used CARs in treating leukemia, and 8 trials in which
CARs were used for solid tumor treatment.

Results: Studies have shown that CARs targeting the B lymphocyte CD19 antigen in
acute hematologic malignancies have a high rate of response (70-90%). Maude et al.
reported that out of 30 patients with acute lymphoblastic leukemia, 27 entered
complete remission. About 50% of patients with chronic leukemia benefit from
CARs. Adverse reactions such as B-cell aplasia can be treated by infusion with
immunoglobulins, and cytokine release syndrome can be managed with anti-IL6R
antibodies. As for solid cancers, the inhibitory tumor microenvironment seems to
represent an obstacle for CARs efficiency. However, some promising results were
reported by Louis et al., 3 out of 19 patients with neuroblastoma entering remission.

Conclusion: Albeit cancer is one of the biggest challenges in medicine, current

research seems to offer promising solutions in finding cures. While further problems
have to be addressed in order to make this therapy reliable, effective and safe, CAR T
cells show extraordinary therapeutic potential.

Keywords: CAR T-cells, immunotherapy, leukemia

SHOULD BE IN POSTERS

The Role of Immunohistochemistry and Dual In Situ Hybridization in Dural

Male Breast Carcinoma Metastasis - Case Presentation

Author: Nicoleta Dumitrescu

Co-Authors: Alexandru Dan Costache, Stefania Teodora Duca
Scientific Coordinators: Alina Paiu, MD, Karina-Anca Bilavschi, MD, Teaching Assistant
Marius Dabija, MD, PhD

Introduction: Breast carcinoma is a very common malignancy in women, but in men it is rare,
accounting for 0.40-0.45% of their cancers. A proper pathological diagnosis of its metastasis
when the primary tumor is not known is paramount since this is needed for an appropriate
treatment.

Material and Methods: To highlight the significance of histological and

immunohistochemical examination, along with Dual In Situ Hybridization (DISH) test in the
case of a male patient who presented an occipital intradural tumor, breast and prostate
neoplasias, and elevated serological Prostatic Specific Antigen (PSA).

Results: We present the case of a 76 years-old male patient, who was admitted in the
Neurosurgery Department with headache, and right hemiparesis for two weeks, with gradual
onset for three months. Physical examination revealed indurate skin of the left breast around
the retracted nipple. Previous medical history revealed a diagnosis of prostate adenoma with
elevated serological Prostatic Specific Antigen(PSA). Cranio-cerebral computed tomography
(CT) examination suspected a meningioma. The tumor was excised and histopathological
examination revealed cords and nests of poorly differentiated epithelial cells embedded into
fibro-vascular stroma. The tumoral cells presented the following immunohistochemical profile:
strong positivity for CK AE1/AE3, estrogen and progesterone receptors; strong focal
expression for Mammaglobin and Gross Cystic Disease Fluid Protein-15 (GCDFP-15);
positivity for PSA; negativity for TTF1, CK7, and CK5/6. Immunohistochemistry also found
out HER2-positive graded as 2+, but DISH test was negative. The final diagnosis was left
occipital intradural metastasis of invasive ductal breast carcinoma with no HER2 gene
amplification.

Conclusion: Dural male breast carcinoma metastasis can express PSA immunopositivity
making the diagnosis more difficult. This immunomarker is only of limited use in differential
diagnosis with prostatic carcinoma metastasis. To correctly diagnose a breast cancer metastasis
in a male patient, a large panel of immunohistochemical stainings along with DISH test should
be used.

Keywords: Male Breast Cancer, Prostate Specific Antigen, HER2 Gene Amplification
Oxytocin, a Potential Adjuvant in Treating Schizophrenia: Review of Literature

Author: Diana Gabriela Scriminti

Co-Author: Raul Alexandru Jigoranu, Tudor Ilie Lazaruc
Scientific Coordinator: Assistant Professor Cristina Furnica, MD, PhD; Teaching Assistant
Lacramioara Perianu, MD, PhD;

Introduction: Schizophrenia(SZ) is a condition that affects the way one thinks and behaves,
social skills and emotional processing. The prevalence is 1% of a countrys population, but
only small fraction is actually diagnosed. Antipsychotic agents are only efficient in improving
positive symptoms (hallucinations), failing in managing hallmarks of a schizophrenic patient
(cognitive deficits,alterated consciousness,its blunt affect).Recent studies indicate Oxytocin
may be useful as an adjuvant in treatment of SZ.Oxytocin is a neuropeptide, which modulates
social behavior and broadens field of perception.It is found in mesolimbic pathway, mainly
inside amygdala, anterior aspect of hypothalamus and olfactory nuclei. Changes in functioning
of these structures are related with negative symptoms genesis.

Material and Methods: We aimed at evaluating the effects of intranasal administration of OT,
as an adjuvant in treating SZ.We propose a systematic review (based on Prisma 2009
guidelines) of related clinical studies published in the past 5 years (2011-2016).We assay both
efficiency and eventual secondary effects of such a treatment.Inclusion criteria were as it
follows: randomized, double-blind, placebo controlled trials, intranasal administration of OT
twice a day, minimum dose of 24 U.I., for at least 14 days, associated with generation II
antipsychotics. Patients were diagnosed with SZ according to DSM IV and symptoms have
been evaluated using same methods: Positive-Negative Symptoms Scale and Theory of Mind
method which determines the cognitive capabilities.Exclusion criteria: more than 20% female
patients participating in the study, patients receiving cognitive-behavioral therapy.
Following a structured search on PubMed and Frontiers, we selected 7 multicenter studies.

Results: Results are strongly dependent on symptoms severity and stage of disease.The
respective positive role as an adjuvant depends on administration schedule.There was no
toxicity after OT intake.

Conclusion: OT improves negative symptoms in SZ and facilitates the social reintegration.

Keywords: Oxytocin, Schizophrenia, Intranasal-Administration

What if You Had a Double Uterus?

Author: Hutanu Andrada

Co-authors: Negura Andreea, Vreme Otilia-Flaviana
Scientific Coordinator: Assistant Professor Alin Horatiu Nedelcu, MD, PhD

Introduction: The congenital uterine abnormalities are usually highlighted in the

medical literature as numerous morphological types. The most common are septate
uterus, bicornuate uterus, arcuate uterus, unicornuate uterus and didelphys uterus. The
last one is an infrequent anatomical pathology pertaining to the unexpected
disconnection of the distal extremity of the mullerian ducts. Taking into consideration
the fact that in the majority of cases, the patients do not experience any symptoms,
this congenital occurence is of great interest amongst surgical and obstetrical world.

Material and Methods: During a regular ultrasonography performed at a 25 years

old woman, two elipsoidally shaped, hyporeflective formations, consisting of
hiperreflective filling have been identified. Consequently, the transabdominal
echography and the endovaginal ultrasound combined with hysterosonography have
been highly appropriate for the uterine abnormalities diagnosis. On the other hand, the
MRI is a more authentic method which offers decisive morphological details and the
cure can be suggested.

Results: The unintentional discovery revealed two uterine disjointed bodies, each of
them having a distinct cervix. The left uterine body is 57mm long and 26mm wide,
with the endometrium of 13mm, whilst the right uterine body is shorter, but wider:
43mm long, 30mm wide and endometrial thickness 11mm. It was also found a typical
ovarian cyst measuring 20mm/18mm.

Conclusion: Uterus didelphys is an uncommon malformation generated by the failure

of fusion of paramesonephric ducts during the intrauterine life. The current scientific
data does not incriminate this malformation as a predisposing factor for the
development of malignancy and neither that it reduces fertility. It is however
associated with a moderate risk of preterm labor and fetal malpresentation at deliver.

Keywords: Uterus Didelphys, Mulerian Ducts, Congenital Uterine Abnormalities

In Vivo and in Vitro Study of Antihypertensive Effects Of NDHP, a New Nitric
Oxide Donor

Author: erban Danciu

Co-authors: Luciano L. Paulo, Maria C. R. Brando
Scientific Coordinator: Professor Valdir A. Braga, DVM PhD

Introduction: Nitric oxide (NO) donors have been used in clinical practice for decades as
therapy in cardiovascular diseases such as arterial hypertension and ischemic heart disease. Our
aims were to evaluate 1,3-bis (hexyloxy) propan-2-yl nitrate (NDHP) as a potential new NO
donor through its effects on cardiovascular system of normotensive and hypertensive rats.

Material and Methods: The concentration-dependent vasodilating effect of NDHP was

quantitatively assessed as maximum effect (ME) in vitro on phenylephrine-(PHE)-
precontracted (10 M) mesenteric artery samples and in vivo using Wistar rats with surgically
induced reno-vascular hypertension (2K1C model) versus normotensive rats (control). After the
6 weeks needed for developing hypertension, polyethylene cannulas were inserted in the
femoral artery and vein for arterial blood pressure measurements and drug injections,
respectively. The blood pressure and heart rate were recorded 24 hours after cannulation and
compared between groups that received NDHP and those that received saline solution.

Results: NDHP (10-1210-3 M) promoted concentration-dependent vasorelaxation in

precontracted mesenteric artery rings isolated from normotensive rats (ME=83.36.7%; n=6).
Furthermore, in normotensive rats, acute administration of NDHP (1; 5; 10; 20 and 40 mg/kg)
constantly decreased blood pressure (-2.30.4; -171; -312; -455; -542 mmHg) while heart
rate measurements showed an initial slight tachycardia in first two doses (+133 and +5715
bpm) followed by significant bradycardia in last three doses (-20229; -28414 and -3089
bpm). Consistently, in conscious hypertensive rats, NDHP (1; 5; 10; 20 and 40 mg/kg) also
decreased blood pressure in a dose-dependent fashion (-82; -154; -443; -615; -621
mmHg, respectively), and induced significant bradycardia in last three doses (-18845; -
30616 and -33415 bpm).

Conclusion: These data show that NDHP is a NO donor which induces vasorelaxation and
presents antihypertensive effects in both normotensive and hypertensive rats. However, more
studies are needed in order to better understand the biochemical pathways involved.

Keywords: nitric oxide donor, NDHP, hypertension

The Importance of Implementing The Correct Wound Care Protocol to Shorten
Wound Healing Time

Author: Melindi Brink

Co-authors: Aamena Osman, Fizah Muratib
Scientific Coordinator: Josephus Daniel Brink, MD

Introduction: Acute wounds are wounds that heal unremarkable within a predicted
amount of time. Chronic wounds begin as acute wounds that end in lengthy recovery
and it is usually accompanied by comorbidities. A UK study revealed the annual
incidence of chronic wounds are 575 600, with a total annual cost of 2.3 3.1 billion
Chronic wounds were reported to be one of the most common cause of morbidity.
All of this proves that to reduce the cost of chronic wounds the treatment aim should
be to reduce the time of healing.The aim is to encourage health care workers to
implement a wound care protocol to reduce the healing time, which will ultimately
reduce the cost of chronic wound care.

Material and Methods: Patients were divided into 2 groups: Group 1 are patients
with chronic wounds and comorbidities and group 2 are patients with acute wounds.
The comorbidities of the patients in group 1 were identified. Then the TIME protocol
is used to make a comprehensive assessment of each wound and determine an
accurate treatment plan.

Results: So far 9 patients have agreed to take part in the study. Out of the 8 patients
with chronic wounds. The TIME protocol was implemented correctly 3 of the 5
patients wounds healed in a significantly shorter time. Out of the 2 patients with
hypertension only 1 had a more rapid healing process. The most significant
improvement can be seen in the patient with both hypertension and diabetes. This
wound persisted for 12 years, but once the protocol was implemented correctly, the
wound healed within 4 months.

Conclusion: By implementing the TIME wound care protocol correctly, the time of
healing of chronic wounds can be significantly reduced.

Keywords: Chronic Wound, Wound Care, Wound Healing Time

New Technologies to Identify Opioids In Biological Samples and to Monitor
The Drug Therapy

Author: Livia Ciubotaru

Co-authors: Diana-Ionela Toia, Ilona Alina Ilie
Scientific Coordinator: Associate Professor Ghiciuc Cristina, MD, PhD

Introduction: The purpose of this study is to show the easy identification of drugs in
biological samples which has been a priority for researchers because of its importance in
treatment management and in forensic medicine. New technologies use minimal noninvasive
ways for drug identification in blood, saliva and urine.
Seventeen basic drugs were identified using Liquid Chromatography- Tandem Mass
Spectrometry which can directly analyze urine for a wide variety of drugs, alongside with
LC/MS/MS.

Material and Methods: There have been used 6 different scientific materials to study the
technologies from different scientific web sites.
Development of Highly Sensitive and Specific mRNA Multiplex System (XCYR1) for
Forensic Human Body Fluids and Tissues Identification: All body fluids were randomly
collected from healthy volunteers.The blood samples were from ten individuals and another
eight individuals provided in conjunction with saliva, oral and nasal swab
samples.
Accumulation of Ractopamine Residues in Hair and Ocular Tissues of Animals during and
after Treatment: A Ridascreen ractopamine kit for ELISA was provided by R-Biopharm
(Darmstadt, Germany). Interpretation of Urine Drug Testing in Pain Patients Central and
Peripheral Metabolic Changes Induced by Gamma-Hydroxybutyrate:. All mice were male and
kept in individual polycarbonate cages under 12 h light/dark cycles, at 25C.

Results: All the subjects that were experimented on have shown a positive result, confirming
the presence of opioids and psychogenic substances through new and innovative methods.

Conclusion: The new technologies can improve the ways we understand the drug overdose in
clinical and forensic fields and also can show in a minimal noninvasive way the drug treatment
evolution, being a revolutionary discovery in modern medicine.

Keywords: Technologies, Opioids, Therapy

The Importance of Scyllo-Inositol in Alzheimers Disease A Literature Review

Author: Marie Pradeau

Co-authors: Omar Zaime
Scientific Coordinator: Lecturer Cristina Mihaela Ghiciuc MD, PhD

Introduction: Alzheimers disease (AD) is a degenerative condition in which destruction of

neurons is progressively occurring by accumulation and aggregation of toxic proteins such as
-amyloid and tau; giving rise respectively to plaques and tangles formation.
Until now, Mild and Moderate staged patients are receiving symptomatic relieving treatment
such as Cholinesterase Inhibitors (Donepezil, Rivastigmine) and NMDA receptor antagonists
(Memantine). Furthermore, Inositol is a compound of six-fold alcohol of cyclohexane and it
exists as nine stereoisomers. Among them, myo-inositol is the most abundant form in the nature
and increased concentrations were found in Cerebrospinal Fluid (CSF) of patients diagnosed
with AD.
On the contrary, Scyllo-inositol (SI) is found rarely in nature and induces a -structure
transition in A42 peptide that did not lead to fibril formation.

Material and Methods: Through systematic literature study, performed on 3 web search
engines, articles related with SI and AD were investigated. Articles which were published
before the year of 2000 were excluded from this review.
Overall, 5 papers were significant for the benefits of SI as a therapeutic agent in AD.
The number of patients, dosage, length of treatment were recorded in order to compare the
effects of this preventive method.

Results: After an average of 76 weeks of treatment with SI at the doses of 1.000 and 2.000 mg,
an increase of brain volume was observed with the use of MRI.
But a dose of 250mg didnt show significant imagistic changes in comparison with the placebo
group. Although, according to Salloway et al, 2011 a decrease of 42 in CSF was measured
at this dosage.

Conclusion: SI seems to be a promising therapeutic agent in AD, although the amyloid-

targeted therapy should be started at earlier stages of this pathology to receive better benefits.
Further studies should be performed in order to corroborate its efficiency.

Keywords: Alzheimer's disease, Scyllo-inositol, Treatment

Anatomic and Morphometric Study of The Mesencephalic Aqueduct

Author: Radu-Cristian Ttaru

Co-authors: Patricia Richter, Eusebiu-Petru Irina
Scientific Coordinator: Teaching Assistant Alin Horaiu Nedelcu

Introduction: The goal of this study is to analize the qualitative and quantitative
evaluation of the cerebral aqueduct, on anatomical pieces.

Material and Methods: The anatomical material used consists of 100 adult brains,
from non-neurological patients. The brains, fixed in formaline solution for 10-16
weeks, were incised medio-sagittal, and the images of the diencephalic-
mesencephalic region, calibrated with the millimeter band, were acquired with the
microscope operator Zeiss and recorded on a Sony F717 video line and digital
camera. The obtained images were computer processed by a technique of classical
linear morphometry.

Results: The qualitative analysis of the cerebral aqueduct allows to generate an

original regionalization in three distinct segments, the longest being the intermediate
segment of passage. The aqueduct extremities were labeled as apertures, rostral and
caudal, and their relationship is precisely described. The quantitative study enables to
establish an anatomical morhometrical standard, and the deviations from the standard
were determined in dolicho-aqueductal sense and respectively brachi-aqueductal. The
comparative study of the anatomical pieces facilitates the production of a basic
material convenient for imagistical data interpretation.

Conclusion: The qualitative and quantitative analysis of the cerebral aqueduct of an

adult, on anatomical pieces, generates the reproduction of a practical regionalization
in assessing the location and the extent of certain diencephalon-mesencephalical
pathological processes.

Keywords: Cerebral Aqueduct, Third Ventricle, Hydrocephalus

497/300! NOT ACCEPTED

Fixed Drug Erythema

Author: Pauna Ana-Maria Raluca

Co-authors: Mihaela Ionela Sirbu, Octavian Carol Mocanu
Scientific Coordinator: Lecturer Elena Cojocaru, MD, PhD

Introduction: Fixed drug erythema reaction is a skin localized reaction that occur after administration of a
drug that can cause the appearance of erythematous maculopapular lesions initially, later pigmentation that
can sometimes evolve to bubble and erosion. Subsequent administration drug can lead to flare the same
location. In the etiology of fixed drug erythema reaction many drugs are criminalized: sulfa antibiotics,
NSAIDs, barbiturates, oral contraceptives and others. The localisation of the lesions are commonly in folds:
bends, popliteal regions, but can be founded in different area of the body. After healing the skin can remain
with hyperpigmentation and postinflamator purple halo.

Material and Methods: We present three clinical cases in which the drugs had lead to fixed drug
erythema.

Results: Clinical Case Nr. 1: sick woman IP aged 24 years, that is working at one office and is also
student, is suffering from headache and abuse consumption of NSAIDs (antinevralgic). She presented to
our service because ten years ago in April shown signs of rhinoconjunctivitis which triggered three years
in the same month a year, how many times the lime flourish in front of the house. The skin testing
sensitization to pollens confirmed the allergy and treatment with antihistamines, specific immunotherapy,
immunomodulation and cutting the tree in the yard led to the disappearance of phenomena. This time the
whole region of the body was covered by numerous interscapular skin pigmentation, round or oval. The
indications was to avoid NSAIDs and food preservatives but the improvement was gradual in the next
three months and disappearance of lesions occurred after seven months, without the consumption of
antinevralgic. Clinical Case Nr.2: Sick man G.G with palm eczema awareness at chocolate comes for the
presence and persistence of approximately 1 year of round spots pigmentation of about 5 cm in diameter,
located in the left arm, at the anterior region of the elbow. The patient initially denied any drug
consumption but I found later he treat himself with iodine. Testing confirmed iodine awareness. Avoid
the use of iodine and treatment with antihistamines, the eruption disappeared in one month. Clinical Case
Nr.3: Sick woman A.I is a clinical case of 26-year that is a professional programmer in England, where
she works for four years, is presented to us with rhinoconjunctivitis phenomena triggered in July and
August. Prick tests confirm the sensitization to grass pollen and institute treatment with antihistamines,
general and local nasal cortisone, nasal anti-inflammatory, immunomodulatory and the indication to
return in November for specific immunotherapy to pollens. At clinical examination, in the arm at 5 cm
distance of the right shoulder a ovalar area of 8 cm in diameter, intensely itchy, more intense nocturnal.
From the anamnesis, the patient take for four years orally contraceptives, at the cutaneous testing, she
was positive at contraceptives. After one year the phenomena dissapeared.

Conclusion: Fixed drug erythema is pathognomonic for drug sensitization. The literature notes that
counterfeit medicines whose active principle did not meet scientific rules produce more quickly fixed drug
erythema.

Keywords: Erythema, Drugs, Lesions

Comorbidities and Polimedication Among Sulfonylurea-Treated Diabetic
Patients: The Risk of Drug Interactions

Author: Luminita Confederat

Co-author: Bianca Profire
Scientific Coordinator: Professor Ctlina Elena Lupuoru, MD, PhD

Introduction: Type 2 diabetes mellitus has become nowadays a major concern considering its
increasing incidence, devastating complications and not at least the costs involved in taking
care of diabetic patients. This chronic metabolic disorder is frequently associated with other
comorbidities which requires the co-administration of different classes of pharmacological
agents, with the risk of drug interactions leading to specific side effects or therapeutic failure.

Material and Methods: The aim of this study was to evaluate the diabetic patients treated
with oral hypoglycemic sulfonylureas related to diseases associated, the concomitantly
administered medications and the risk of drug interactions. Materials and Methods: A
retrospective study which included 50 diabetic patients under treatment with sulfonylureas
was performed. Information concerning patient characteristics, the presence of other
comorbidities and drugs taken simultaneously with hypoglycemic treatment and side effects
reported were obtained from the observation sheets; data were analyzed, statistically
processed and interpreted using MS Excel software. Results and discussions: The age of the
patients studied ranged between 52 and 88 years, with an average of 62.44.3 years. The
study group presented a balanced repartition by gender and the majority of them came from
urban areas.

Results: Hypertension was the most common disease associated with diabetes (68%), followed
by different forms of dyslipidemias (53.5%). The hepatic dysfunctions, the rheumatologic
diseases and the digestive disorders were other pathologies associated to studied patients. The
drugs more frequently associated with the antidiabetic treatment were 1-receptor blockers,
ACE inhibitors, fibrates and NSAIDs. These drugs have presented a high risk of interactions
with sulfonylureas and the main result was hypoglycemic accidents, with a frequency of 9%.

Conclusion: Considering the complexity of the comorbidities associated with studied diabetic
patients and related to it the necessity to use drugs with different pharmacokinetic and
pharmacologic profile, the risk of drug interactions and their consequences should be taken into
account.

Keywords: Diabetic Patients, Comorbidities, Drug Interactions

The Promise of Senolytic Drugs in Recovering The Healthy Immune Response
For Elders

Author: Claudia Ileana Mihailescu

Co-authors: Anca Nicolae, Irina Dicea
Scientific Coordinator: Alexandru Ioan Voda

Introduction: Gradual decay of the immune system takes place over time in humans.
This problem exposes elders to harsh or even deadly episodes of otherwise non-lethal
infections. New evidence from multiple research groups strongly suggests that the
accumulation of senescent cells with aging plays a major negative role in immune
physiology. Eliminating these cells in aged mice restored their capacity to respond
adequately to infections that have debilitating effects on age-matched controls.

Material and Methods: The three most recent studies were chosen and ranked based
on their methods of generating the models, drug vectors and other features.
Additionally, their screening processes have been contrasted with two new
bioinformatic methods from other unrelated studies.

Results: All models show great improvements in a range of health metrics. A single
administration of senolytics is enough to recover the healthy response in treated
models. The treated groups also gain longer lifespans on average. Dasatinib and
quercetin, due to their prior FDA and EMA approvals, show a particularly strong
potential for clinical use. The observed side-effects are much under the expected
amplitudes for the therapeutical doses.

Conclusion: Current evidence strongly suggests that the senescent cells of the
immune system cause a few age-related pathologies. Previously approved selective
pro-apoptotic drugs show great promise for treatment. While accelerating research on
rejuvenating the immune system is tempting indeed, planning and caution should be
key in developing a safe drug that can move into clinical trials.

Keywords: Aging, Immunity, Senolytics

NOT ACCEPTED

VMAT2 - The God Gene, A Great Contribution Or A Great Controversy?

Author: va Dvid
Co-authors: Carina Eleonora Gherc, Roxana Rtan
Scientific Coordinator: Lcrmioara Butnariu, MD

Introduction: The knowledge of human genome has increased the curiosity of

students about the roles that genes and the environment play in determining human
characteristics.

Material and Methods: The press often debates the influence of genes on diseases,
such as cancer or personality traits such as sexual orientation. In response, people
took different stands at one extreme, some of them engaged in genetic
determinism, at the other extreme, others rejected any role of genetics in human
behavior as incompatible with free will. Dean Hamers book, The God Gene: How
Faith is Hardwired into Our Genes, points out a link between a gene and human
behavior. VMAT2 (vesicular monoamine transporter 2) gene encodes a transporter
protein that is responsible for the packaging of neurotransmitters such as dopamine,
serotonin, norepinephrine and epinephrine into synaptic vesicles.
VMAT2 became an important pharmacological target for the discovery of novel
therapeutics to treat drug addiction.

Results: The monoaminergic neuron, in particular the dopaminergic neuron, is

central to mediating the hedonic and addictive properties of drugs of abuse.
Whether VMAT gene is a God gene or not is a matter of interpretation.

Conclusion: The point is we have discovered inside of us a weapon for treating

addiction and affective disorders and we have a powerful reason to keep up the fight.

Keywords: Gene, VMAT2, Neurotransmitters

A Step Closer to Personalized Medicine. Is miRNA The Future of Diagnosis in
HCC

Author: Maria Alexandra Chiriac

Co-authors: Alexandra-Evelina Ciubotariu, Alexandru Trenchea
Scientific Coordinator: Teodora Alexa Stratulat, MD

Introduction: HCC (hepatocellular carcinoma) is the second cause of cancer death

worldwide with chronic hepatitis B (HBV) being the leading risk factor. However
HBV- related HCC is often detected late, when surgical interventions and liver
transplantation are no longer feasible thus making early diagnosis extremely
important. Curently alpha-fetoprotein (AFP) is used for screening with a sensitivity
65% and specificity 75%. MicroRNAs (miRNAs) are a group of regulatory
noncoding RNA molecules that can be used as biomarkers for the diagnosis and
prognosis of HCC. The aim of the study is to asses the benefit of using circulating
miRNA as biomarkers from both efficency and economic stand point.

Material and Methods: A sistematic literature review was performed and resulted in
433 studies that mentioned miRNA as biomarkers for HCC. Of these, 31 were
specifically regarding HBV related HCC.

Results: A total number of 76 miRNA were found with 45 being upregulated and 31
down regulated. After extensive reading 10 miRNA were found used more often with
miRNA-122 frequently noted. All studies have assesed the ability of using miRNA as
biomarkers with a sensitivity and specificity up to 85-97% in discriminating HCC
from healthy controls. Furthermore,with only $0.39 per sample using q-PCR with
NGS (next generation sequencing) or $5.88 using standard q-PCR, the use of miRNA
as biomarkers is cost effective.

Conclusion: Due to their high specificity and sensitivity, miRNA can be used as
biomarkers in the early detection of HCC. The use of these represents an advantage
not only from the economic point of view, but also from a medical point of view for
early detection of HCC will significantly increase the survival rate of patients.

Keywords: miRNA, hepatocellular carcinoma, biomarkers

Ultrastructural Modifications Specific to Premalignant Skin Lesions

Author: Catalina Gabriela Popovici

Co-author: Ioana Adriana Serban
Scientific Coordinator: Teaching Assistant Doinia Olinici, MD, PhD; Professor
Carmen Cotrutz, MD, PhD;

Introduction: A premalignant lesion is that lesion which in absence of any kind of treatment
presents a high risk of malignant transformation. Over the years, a rise in the prevalence of
premalignant skin lesions has been observed, especially precursors of scuamocellular
carcinomas. Among these, actinic keratosis presents the highest risk of malignant
transformation.

Material and Methods: The anatomopathological diagnosis of these lesions, using

hematoxylin-eosin staining, does not highlight specifically all the modifications of the
structures of the cell, such as the membrane, organites and some elements of the extracellular
matrix. Consequently, the present study uses the transmission electron microscopy technique to
highlight ultrastructural alterations characteristic to this pathology.
Cutaneous fragments were harvested from 10 patients diagnosed with actinic keratosis. These
fragments were then classically prepared for examination with the transmission electron
microscopy technique. The microscope used was a Philips CM100.

Results: Morphological aspects of the examined tissue, observed using the optic microscope,
were confirmed by the examination using the transmission electron microscope. Additionally,
the second examination offered important ultrastructural information regarding the epithelial
dysplasia, characteristic to these lesions. Thereby, the observed enlargement of intercellular
spaces (not an artefact of processing), alongside the disorganization of cell-cell and cell-matrix
areas, mitochondrial degeneration which indicates a deficient cellular energy, nucleo-nucleolar
modifications, increase in the number of ribosomes, modifications of the basal membrane (its
detachment from the epithelial cells, the presence of residual material in lamina propria) are
just some of the aspects revealed from the transmission electron microscopic study. On one
hand they indicate the tendency of malignant transformation and on the other hand most of
them represent characteristics in tumour development.

Conclusion: The ultrastructural details provided by the transmission electron microscopy

complete the chart of morphological modifications specific for these lesions, indicating the
importance of utilising this technique in establishing a certain diagnosis and a correct
prognostic.

Keywords: Electron Microscopy, Actinic Keratosis, Ultrastructure

Study on The Incidence, Prevalence and Evolution of Multi Drug (MDR-TB) and
Extensively Drug-Resistant Tuberculosis (XDR-TB)

Author: Traian Chiuariu

Co-authors: Alexandra Cecilia Coru
Scientific Coordinator: Teaching Assistant Ctlina Lunc, MD

Introduction: Tuberculosis (TB) is an infectious disease which has been drawing

attention over the past years because of the ability of its etiologic agent
(Mycobacterium tuberculosis) to gain resistance to two first line antibiotics used in
therapy (rifampicin and isoniazid) which leads to multi drug-resistant tuberculosis
(MDR-TB). The mismanagement of MDR-TB can turn it into an even more resistant
form - extensively drug-resistant tuberculosis (XDR-TB). If drug-susceptible TB can
be treated successfully in approximately 6 months, in the case of MDR-TB the
chances of success are 50%, while for XDR-TB the chances drop to 25%, and the
time needed for cure rises to 24 months, with huge costs.

Material and Methods: The study was relied on surveillance reports of World
Health Organization and European Centre for Disease prevention and Control
regarding the incidence, prevalence and treatment outcomes of MDR-TB and XDR-
TB cases, in Romania, European Union and worldwide between 2006 and 2016.

Results: The results of the study showed an alarming aspect, given the fact that the
number of cases of drug-susceptible TB was decreasing, but the numbers of MDR-TB
and XDR-TB cases were increasing. This situation leads to lower rates of treatment
success and increasing costs of therapy.

Conclusion: These data support the need for improved management of TB cases
through the use of rapid diagnostic methods, increased patient compliance to
treatment and efficient prevention.

Keywords: Tuberculosis, Drug Resistance, Management

Experimental Skin Cancer Models On Mice - Critical Considerations Regarding
Treatment

Author: Junca Victor-Mihai

Co-authors: Siriteanu Emanuel-Andrei, Dobrisan Bianca-Teodora
Scientific Coordinator: Professor Catalina Elena Lupusoru, MD,PhD; Associate
Professor Lacramioara Ochiuz, MD, PhD; Associate Professor Cristina Mihaela
Ghiciuc, MD, PhD;

Introduction: Skin cancer, with an increasing incidence over the years (6% per year), develops
frequently from precancerous lesions. There are complex interferences induced by intrinsic
(genetic, immunologic, metabolic), or extrinsic (UV-R, repeated traumas) factors. The aim of
our paper was to critically evaluate the experimental skin cancer model on mice for an
appropriate use for studying the effect of preventive or curative treatments.

Material and Methods: Data sources were experimental articles and critical reviews about
skin cancer models in mice from PubMed, published from 1970 to 2017. From 224 papers,
there were selected 163 for our study. There were excluded letters to the editors and
commentaries. Two methods are used to induce skin carcinogenesis, chemical and physical,
each one having a distinctive treatment based on the type of cancer developed and harshness of
lesions.

Results: Differences between these methods of inducing carcinogenesis are relative in terms of
times of exposure, the key factors being the number of doses, the quantity of each
dose and the frequency of administration, the inductor type. At a molecular level, chemical
induction produces the mutation of the Ha-Ras oncoprotein, whereas UV-R generates
mutations in TP53. Knowing the molecular level at which the lesions are made, there have been
reported over 30 compounds and methods (Silymarin, Resveratrol, Sanguinarine, Honokiol,
genetical engineered p53) that have been used on animal models for the prophylaxis or healing
treatment of non-melanoma skin cancer, the most frequenctly being SCC.

Conclusion: Animal models have a crucial role in experimental research, especially in the
development of new therapeutic strategies.
Essential in selecting the best model for research and especially for testing new drugs for
treatment of cutaneous cancer is to know the limits and the strengths of various animal models.

Keywords: Skin Cancer Treatment, Chemically Induced, Irradiation Induced

The Broad Spectrum of BDNF Gene Expression Abnormalities in Neuronal
Development, Memory and Learning Processes

Author: Ruxandra Lazar

Co-author: Andrada Hutanu
Scientific Coordinator: Lecturer Lavinia Caba, MD, PhD

Introduction: Mechanisms underlying memory and learning involve a gene

expressed protein known as brain derived neurotrophic factor (BDNF) which also
plays a key-role in the pathophysiology of many neurodegenerative and psychiatric
disorders such as schizophrenia, Alzheimers and Huntingtons disease.

Material and Methods: The hippocampus and the amygdala have been directly
related to memory encoding, but the neural wiring functions are modulated by BDNF
secretion. The activity of the TrkB (receptor for BDNF) is linked to synaptic plasticity
which is decisive in storing information. It has been found that the TrkB
phosphorylationdeficient mice displayed impaired spatial memory and compromised
hippocampal long-term potentiation. Variations in the BDNF gene have a significant
effect on memory performance, and on both the structure and physiology of the
hippocampus.

Results: The lower serum levels of the protein were connected to reduced areas in
hippocampus, whereas higher serum BDNF levels seem to be protective against
developing dementia. Reduced expression of BDNF has been noticed in a region that
is vulnerable to neuronal loss in Parkinsons disease. Most roles of BDNF in the
memory and learning processes depend on the interaction with two different
transmembrane receptors localized to dendrites, axons and soma of neurons.

Conclusion: Although drugs with different BDNF doses would seem to be a

symptomatic treatment for neurodegenerative diseases, transforming them into a
clinical application makes it difficult due to poor pharmacokinetics and limited
diffusion of BDNF. In conclusion we present a synthesis of the role which the BDNF
gene has in the pathogenesis of the neurodegenerative and psychiatric diseases as well
as the clinical appliance of the functional product of the gene in treatment.

Keywords: BDNF, Memory, Neurodegenerative Disorder

Special Stains In Histology And Histopathology From Principles To Practice

Author: Profire Bianca-Stefania

Co-author: Balan Teodora
Scientific Coordinator: Professor Irina Draga Cruntu, MD, PhD

Introduction: The special stains consist of the ensemble of alternative staining

methods and histochemical procedures exploit to complement the morphological
information usually provided by the common, routine hematoxylin-eosine (HE) stain.
They are useful to identify normal or abnormal substances existing in certain cells
and/or components of tissues, but not visible in HE. The understanding of the
chemical principles that conduct to the final coloured product is important in the
current practice of histology and histopathology.

Material and Methods: The material was represented by specimens corresponding to

the four fundamental tissues (epithelial, connective, muscular and nervous) and
pathological lesions. We performed the following special stains: PAS (Periodic Acid
Schiff), trichrome (with light green and aniline blue, respectively), Alcian Blue,
Cresyl Violet, orcein, Congo Red, Perls, Fontana.

Results: The appliance of the special stains allowed the recognition of the following
normal morphological entities: goblet cells in intestinal epithelium, mucous acini in
salivary glands, extracellular matrix in connective tissue, muscle cells in the wall of
cavitary or tubular organs, Nissl bodies in neurones. Moreover, they permitted a clear
separation of the arterial layers, the recognition of the basement membrane and,
respectively, amyloid deposits in renal corpuscles, the differentiation between
hemosiderin and melanin pigment in melanoma,
the confirmation of mucine secretion that characterizes several malignancies.

Conclusion: The special stains offer reliable knowledge about numerous cellular and
matrix elements belonging to the complex tissue framework in normal and
pathological status, while ensuring an increased accuracy in addressing common
diagnostic problems.

Keywords: special stains, histology, histopatology

Teratogenic Effects Of The Zika Virus

Author: Andreea Onofrei

Co-author: Victor Daniel Miron, Dragos Andrei Marin
Scientific Coordinator: Assistant Biologist Madalina Mioara Miron

Introduction: Zika virus is a mosquito-borne flavivirus that has emerged as a

significant global treath, especially to pregnancy. The first trimester of pregnancy is a
crucial period for organogenesis and has become clear a strong causal relationship
between Zika virus infection during pregnancy and the occurrence of microcephaly,
fetal growth restriction and eye defects.

Material and Methods: By using the search terms "zika virus" and "pregnancy" on
PubMed and narrowing the search down to the publication timespan January 2015 -
February 2017, we have identified 33 studies that describe the pathogenical
mechanisms involved in the Zika virus-associated embryopathy.

Results: Recent papers support different hypothesis involved in the development of

neurological abnormalities that include Zika virus infection-induced damage to the
liver associated with toxic retinoids concentrations in maternal and fetal circulation
and damage to the human placental barrier with the early onset of TORCH-type
chronic placentitis. Research performed on both infected mice and aborted fetuses
revealed neuronal degeneration and softening of the brain with virus replication in
astroglial cells and neurons. Interestingly, there was no evidence of virus presence or
pathological changes in other organs so it was concluded a strong neurotropism of the
virus. Moreover, exposure to Zika virus in pregnancy was associated with severe fetal
ocular findings (such as chorioretinal atrophy and optic nerve abnormalities) and
Guillain-Barre syndrome, a serious complication that often evolves into paralysis.

Conclusion: By analyzing the specialty literature that encompasses both clinical and
paraclinical data, we determined that the Zika virus, as a pathogen that fully meets the
teratogenicity criteria set proposed by Shepard, is strongly linked with microcephaly
and other significant congenital anomalies. In such circumstances, further research in
the development of vaccine, diagnosis and treatment methods becomes compulsory.

Keywords: Zika Virus, Microcephaly, Teratogenic Effects

NT-proBNP in Congestive Heart Failure

Author: Ilascu Bianca Mara

Co-authors: Teodorescu Eugen, Varlam Corina
Scientific Coordinator: Raluca Ecaterina Haliga, MD

Introduction: Congestive heart failure is a functional syndrome, defined as the incapacity of

the heart to assure a fine circulation in the body. It represents one of the main causes of
morbidity and mortality and the prevalence of this disease is increasing at old people.

Material and Methods: The study group was represented by 30 pacients with different grades
of heart failure severity (first group 12 pacients with heart failure class II NYHA and the
second group 18 pacients with heart failure class III NYHA), admitted in Sf. Spiridon
hospital for observation. We analyzed the following parameters: heart failure incidence
according to sex and age; identifying risk factos at the pacients with CHF; highlighting a
correlation between the N-terminal fragment of B-type natriuretic peptide (NT-pro BNP) and
risk factors, the degree of anemia and diselectrolitemia. The data were processed using SPSS
18.0 statistical functions significance threshold of 95%, using as indicators derived from those
described ANOVA.

Results: We found that the incidence of CHF is 1.56 times higher in men compared to the
women and the average age was 70.37 11.01 years. Patients have accused exertional dyspnea
and chest pain more often in those with NYHA class II CHF , in patients with NYHA Class III
CHF favoring resting dyspnea, palpitations and edema. At patients with atrial fibrillation
diastolic diameter (DTDVS) and systolic (DTSVS) of the left ventricle were recorded
significantly higher average values when compared to the patients with sinus rhythm. NT-
proBNP correlation between hemoglobin level (r = -0.714; R2 = 0.5097; p = 0.001), hematocrit
(r = -0.711; R2 = 0.5049; p = 0.001) and red blood cell counts (r = -0.645 R2 = 0.4154; p =
0.001) was indirect.

Conclusion: The relative risk of severe CCI is higher in males and the elderly associating
arrhythmias, atrial fibrillation is the most common. Patients with atrial fibrillation and drinkers
recorded averages slightly elevated NT pro-BNP. DTDVS and DTSVS are significantly
elevated in patients with atrial fibrillation, with elevated NT pro-BNP and drinkers.

Keywords: NT-proBNP, congestive heart failure

The Importance of Chromosomal Analyse In Diagnosing Of
Plurimalformative Syndromes

Author: Oana - Cornelia Gorduza

Co-author: Diana Iosep, MihneaMiron
Scientific coordinator: Assistant Professor Lavinia Caba MD PhD

Introduction: Congenital anomalies are morphological defects produced during prenatal

period and present at birth. The chromosomal etiology is a crucial factor in their diagnosis. We
present 3 cases of unbalanced chromosomal selected from archive of Medical Genetics
Department of"Cuza-Voda" Obstetrics and Gynecology Iasi.

Materials and methods: First Case: newborn boy, 1 day old, born at term, after a pregnancy
without follow-up. Weight=2450 g, Length=42 cm. The plurimalformative syndrome was
characterized by: short stature, muscular hypotonia, craniofacial dysmorphia (prominent
occiput, hypertelorism, microstomy, micrognathism), I - II syndactyly in feet, undescended
testis, micropenis, hypospadias. Chromosomal formula: 46,XY,der(7)t(7;4)(q36;q27).
Second Case: girl, 4 days old, born at 38 weeks of amenorrhea, with a poor intrauterine growth,
W=1400 g, L=46 cm, head circumference = 28 cm, thoracic circumference = 26 cm, muscular
hypotonia, plurimalformative syndrome: facial dysmorphia (microcephaly, microphthalmia,
short philtrum, ogival palate, microretrognathism, low-set ears), short neck, II - III syndactyly
in feet, ventricular septal defect, underdeveloped external genitalia, labial hypoplasia.
Chromosomal formula: 46,XX,der(4)t(4;10)(q35;q22.1). Third Case: boy, 2 days old, born at
39 weeks of amenorrhea, with a poor intrauterine growth, W=1600 g, L=42 cm, head
circumference = 28 cm, muscular hypotonia, plurimalformative syndrome: facial dysmorphia
(microcephaly, dolichocephaly, hypertelorism, long philtrum, micrognathism, ogival palate,
low-set ears), short neck, micropenis, cardiac malformations (left ventricle diastolic
dysfunction, patent arterial duct, patent foramen ovale). Chromosomal formula:
46,XY,r(13)(p11.2q34)/45,XY,-13.

Results: The chromosomal analyze was applied in the parents of the children. The mother of
second case presented a balanced reciprocal translocation: 46,XX,t(4;10)(q35;q22.1), which
indicates a risk of maximum 7,5% to have another infant with the same anomaly.

Conclusion: It is essential to perform chromosomal analyses in case of plurimalformative

syndromes for establishing the correct etiology and accord a correct genetic counseling.

Keywords: Plurimalformative Syndrome,Unbalanced Chromosomal Abnormalities,Genetic

Counseling