Clinical and molecular analysis of common MEFV gene mutations in familial Mediterranean fever in Sivas population

Familial Mediterranean fever (FMF) is the most frequent hereditary inflammatory disease characterized by self-limited recurrent attacks of fever and serositis. The aim of the current study is to determine the frequency of the mutations in 365 suspected FMF patients and to reveal whether there is a correlation between genotype and phenotype of these patients. All patients were clinically examined according to Tell-Hashomer FMF criteria and were screened genetically in terms of common 12 Mediterranean fever gene (MEFV) mutations. Various point mutations were detected in 270 (74%) patients. The most frequent mutation was M694V (26.85% of the alleles) and was followed by E148Q (15.55%), M680I (G/C) (9.62%) and V726A (7.96%). Patients who bear M694V homozygous mutation had most severe disease phenotype and high risk for amyloidosis (P = 0.04). Our results indicate that Sivas population has a wide range of heterozygous mutated carriers of MEFV gene and there is a high frequency of E148Q allele when compared to the other Mediterranean groups.     

The infection risk of visceral leishmaniasis among household members of active patients

Human visceral leishmaniasis (HVL), caused by Leishmania infantum is mainly observed as sporadic cases in Turkey and dogs are considered as the main reservoir of the disease. The incidence of visceral leishmaniasis among members of households where a HVL infection has already been diagnosed was studied in clusters around the diagnosed cases in different regions in Turkey. A total of 47 serum samples collected from the households of 11 proven visceral leishmaniasis patients were screened for anti-Leishmania antibodies by indirect immunofluorescent antibody test (IFAT). Three and one such household members belonging to the different families were found to be seropositive and borderline, respectively. Diagnosis was confirmed with the presence of amastigotes in bone marrow aspiration samples in all seropositives while the borderline case with slight and indefinitive symptoms of VL was followed only serologically at 3-month intervals and improved spontaneously in 1 year. Household members of individuals with previously confirmed visceral leishmaniasis were found to have higher frequency of the disease suggesting the household members should be included in the risk group for visceral leishmaniasis and serological screening should be performed for the detection of possible infection.     

The effects of chronic exposure to ethanol and cigarette smoke on the formation of peroxynitrite, level of nitric oxide, xanthine oxidase and myeloperoxidase activities in rat kidney

The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Rats in E, CS and CS+E groups were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys were removed to determine the activity of xanthine oxidase (XO), myeloperoxidase (MPO) and the levels of nitric oxide (NO). Histopathological and immunohistochemical analysis were performed in kidney tissues. The activity of XO/g protein were 2.8 ± 0.3, 5.2 ± 0.3, 3.2 ± 0.1, and 7.4 ± 0.7 U for C, E, CS and CS+E groups, respectively. In groups E, and CS+E, the XO values were significantly higher than in group C (P < 0.05). The increase in XO activity of CS was not significantly different from group C (P > 0.05). There was a significant increase in XO activity of group CS+E as compared to CS and E groups (P < 0.05), and also a significant difference in XO activity between E and CS was observed (P < 0.05). The activity of MPO/g protein were 13.5 ± 0.6, 16.2 ± 1.1, 14.7 ± 1.1, 23.8 ± 0.9 U for C, E, CS, and CS+E groups, respectively. While MPO activity of kidneys from group CS+E were significantly higher as compared to C, CS, and E groups (P < 0.05), there was no significant difference among the groups of C, CS, E (P > 0.05). The levels of NO/g wet tissue were 347.7 ± 8.5, 261.1 ± 4.8, 329.8 ± 5.6, and 254.2 ± 3.8 nmol for C, E, CS, and CS+E groups, respectively. In groups of E and CS+E, the NO values were significantly lower than that of group C animals (P < 0.05). Although we detected lower NO levels in the E and CS+E groups than in CS group (P < 0.05), a significant difference in NO levels between CS+E and E groups was not observed. In the histopathological analysis of the kidney slices, severe degenerations in kidney tissues of group CS, E, CS+E were observed. Generally, the histological changes in kidney of CS+E and E groups were more severe than those observed in CS alone. While we observed a strong immunoreactivity for anti-nitrotyrosine antibody in kidneys of group CS+E, examination of sections from rat kidneys in group E revealed moderate staining. On the other hand, group CS had very little immunostaining. There was no immunostaining in group C.We concluded that chronic ethanol administration and cigarette smoke exposure may cause oxidative and nitrosative stress which lead to rat kidney damage.     

Integration and segregation of activity in entorhinal-hippocampal subregions by neocortical slow oscillations

Brain systems communicate by means of neuronal oscillations at multiple temporal and spatial scales. In anesthetized rats, we find that neocortical "slow" oscillation engages neurons in prefrontal, somatosensory, entorhinal, and subicular cortices into synchronous transitions between UP and DOWN states, with a corresponding bimodal distribution of their membrane potential. The membrane potential of hippocampal granule cells and CA3 and CA1 pyramidal cells lacked bimodality, yet it was influenced by the slow oscillation in a region-specific manner. Furthermore, in both anesthetized and naturally sleeping rats, the cortical UP states resulted in increased activity of dentate and most CA1 neurons, as well as the highest probability of ripple events. Yet, the CA3-CA1 network could self-organize into gamma bursts and occasional ripples during the DOWN state. Thus, neo/paleocortical and hippocampal networks periodically reset, self-organize, and temporally coordinate their cell assemblies via the slow oscillation.     

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid–base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.