CHROMOSOMAL ABNORMALITIES AND Y CHROMOSOME MICRODELETIONS IN BULGARIAN MALE WITH AZOOSPERMIA OR SEVERE OLIGOSPERMIA

Male infertility is a complex disease, and genetic abnormalities are among the main causal factors for the disorder. Aim: In order to evaluate the proportion of the most common genetic factors in etiology of male infertility, examination for chromosomal abnormalities and microdeletions of Yq chromosome (delYq) was carried out in Bulgarian males with severe infertility. Materials and methods: The study was retrospective and involved a total of 142 infertile Bulgarian males (63 patients with azoospermia and 79 patients with severe oligozoospermia /sperm count < 5×106/ml), referred (2007-2016) for genetic testing, after preliminary examinations to exclude some more frequent causes for male infertility. Cytogenetic analysis by GTG-banding was carried out in 137 men, and molecular testing for AZF region microdeletions of Y chromosome by multiplex PCR was carried out in 109 men. Results: Chromosomal abnormalities were found in 16.8% of all investigated infertile men and the frequencies in patient subgroups with azoospermia and oligozoospermia were 20.7% (12/58) and 13.9% (11/79) respectively. The established frequency of delYq was 5.5% (6/109) in the overall group of infertile male and higher - 9.5% (6/63) in a subgroup of patients with azoospermia.The overall proportion of the two genetic factors was 30.2% in patients with azoospermia and 14% in men with oligozoospermia. In conclusion, chromosomal abnormalities and delYq account for about 22% of cases with severe infertility in Bulgarian men. Genetic testing should be a routine part of examinations in infertile males and along with genetic counseling; they provide an opportunity for the best choice of an appropriate technique for assisted reproduction of the couples

Multidisciplinary approach to management of hypofibrinogenaemia in pregnancy: A case report

Inherited fibrinogen disorders introduce risk for recurrent abortions, sub-chorionic haematoma, placental abruption and postpartum haemorrhage. This is a case report of a successful pregnancy outcome in a 37-year old woman with hypofibrinogenaemia. She was referred to a coagulation test in the first trimester because of history of preeclampsia and HELLP syndrome in previous pregnancy. Hypofibrinogenaemia was diagnosed with fibrinogen level of 0.7 g/L. During the pregnancy she was regularly monitored for fibrinogen levels and multiple cryoprecipitate concentrates were given. She delivered at 39th gestation week, with elective caesarean section under general anaesthesia. There was one episode of postpartum haemorrhage treated with 2 units of red blood cells, repeated infusions of cryoprecipitate to obtain the level of fibrinogen of 2 g/L. She was discharged on the 6th postpartum day in a good condition. In these disorders levels of fibrinogen should be higher than 1 g/L during pregnancy or 2 g/L in case of caesarean section for successful prenatal and peripartal management

Recent Advances in Anti-Tuberculosis Drug Discovery Based on Hydrazide–Hydrazone and Thiadiazole Derivatives Targeting InhA

Tuberculosis is an extremely serious problem of global public health. Its incidence is worsened by the presence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. More serious forms of drug resistance have been observed in recent years. Therefore, the discovery and/or synthesis of new potent and less toxic anti-tubercular compounds is very critical, especially having in mind the consequences and the delays in treatment caused by the COVID-19 pandemic. Enoyl-acyl carrier protein reductase (InhA) is an important enzyme involved in the biosynthesis of mycolic acid, a major component of the M. tuberculosis cell wall. At the same time, it is a key enzyme in the development of drug resistance, making it an important target for the discovery of new antimycobacterial agents. Many different chemical scaffolds, including hydrazide hydrazones and thiadiazoles, have been evaluated for their InhA inhibitory activity. The aim of this review is to evaluate recently described hydrazide-hydrazone- and thiadiazole-containing derivatives that inhibit InhA activity, resulting in antimycobacterial effects. In addition, a brief review of the mechanisms of action of currently available anti-tuberculosis drugs is provided, including recently approved agents and molecules in clinical trials

In Vivo Toxicity, Redox-Modulating Capacity and Intestinal Permeability of Novel Aroylhydrazone Derivatives as Anti-Tuberculosis Agents

The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further development. Here, we present the aroylhydrazone compounds (3a and 3b) regarding their: (i) acute and subacute toxicity in mice; (ii) redox-modulating in vivo and in vitro capacity; (iii) pathomorphology in the liver, kidney, and small intestine tissue specimens; and (iv) intestinal permeability. The acute toxicity test showed that the two investigated compounds exhibited low toxicity by oral and intraperitoneal administration. Changes in behavior, food amount, and water intake were not observed during 14 days of the oral administration at two doses of 1/10 and 1/20 of the LD50. The histological examination of the different tissue specimens did not show toxic changes. The in vitro antioxidant assays confirmed the ex vivo results. High gastrointestinal tract permeability at all tested pH values were demonstrated for both compounds. To conclude, both compounds 3a and 3b are highly permeable with low toxicity and can be considered for further evaluation and/or lead optimization

Abstracts Of The Proceedings And The Posters From The Third Scientific Session Of The Medical College Of Varna

October 2-3, 201