GENOTYPIC DISTRIBUTION OF HPV AMONG WOMEN OF REPRODUCTIVE AGE IN GEORGIA.

Of the 100 types of human papillomaviruses (HPV), approximately 35 infect the genital tract. The viruses are categorized as "high risk" and "low risk" depending on whether they are known to cause cancer or not. Cervical cancer is an important cause of cancer mortality in Georgia, and worldwide. Only limited and incomplete data are available about the epidemiology of HPV infection and related molecular and cellular changes in Georgia. Objectives of our study included the estimation of the prevalence and the distribution of HPV genotypes among women in Georgia. The study participants were women (~2000) aged 18-49 years randomly selected during a clinic appointment with a gynecologist for a regular check-up at one of the women's consultation centers (WCC) participating in the study. Venous blood (5 ml) was drawn and the prevalence of HPV evaluated by the detection of the HPV DNA. For genotyping, HPV DNA were extracted from the cervical samples, amplified first by consensus and then by primer-specific PCR, followed by a detection step on agarose gel. Of the total samples, 250 were positive for HPV DNA; these were further tested to identify the specific HPV genotype. The genotype distribution was as follows: type 6, 98 women (39.2 %); type 16, 64 (25.6%); type 18, 47 (18.8%); type 33, 23 (9.2%); type 11, 27 (10.8%); type 45, 19 (7.6%); and type 66, 9 (3.6%). In 37 women (14.8%), we found coexistence of several different HPV genotypes. The HPV genotypic profile among Georgian women is similar to data generated from studies conducted among the populations in other European countries. Presence of the subset of HPV genotypes not covered by quadrivalent anti-HPV vaccine (types 33, 45 and 66) was demonstrated among Georgian women.

DREADDs suppress seizure-like activity in a mouse model of pharmacoresistant epileptic brain tissue.

Epilepsy is a neurological disorder with a prevalence of ≈1% of general population. Available antiepileptic drugs (AEDs) have multiple side effects and are ineffective in 30% of patients. Therefore, development of effective treatment strategies is highly needed, requiring drug-screening models that are relevant and reliable. We investigated novel chemogenetic approach, using DREADDs (designer receptors exclusively activated by designer drugs) as possible inhibitor of epileptiform activity in organotypic hippocampal slice cultures (OHSCs). The OHSCs are characterized by increased overall excitability and closely resemble features of human epileptic tissue. Studies suggest that chemically induced epileptiform activity in rat OHSCs is pharmacoresistant to most of AEDs. However, high-frequency electric stimulus train-induced bursting (STIB) in OHSCs is responsive to carbamazepine and phenytoin. We investigated whether inhibitory DREADD, hM4Di, would be effective in suppressing STIB in OHSC. hM4Di is a mutated muscarinic receptor selectively activated by otherwise inert clozapine-N-oxide, which leads to hyperpolarization in neurons. We demonstrated that this hyperpolarization effectively suppresses STIB in mouse OHSCs. As we also found that STIB in mouse OHSCs is resistant to common AED, valproic acid, collectively our findings suggest that DREADD-based strategy may be effective in suppressing epileptiform activity in a pharamcoresitant epileptic brain tissue.

Effect of oleamide on pentylenetetrazole-induced seizures in rats.

Oleamide exhibits antiepileptic activity and significantly decreases the degree of pentylenetetrazole-induced seizures.