Regulatory Challenges in the COVID-19 Era: The Case of Tunisia.

In view of the possible disruptions in the manufacturing and supply of health products following the coronavirus disease 2019 (COVID-19) pandemic, the Tunisian medicines regulatory authority was mobilized to guarantee patient safety. Teleworking has become the ultimate way of service continuity. The planning was revised according to health priorities. Work procedures were set online. A minimum list of medicines known as "medicines of health and strategic interest" was established. The Directorate of Pharmacy and Medicines (DPM) has been working on updating medicines stock data. A provisional suspension of authorizations for medicines export for 1 mo was decided. A fast-track procedure allowing the validation of alternative sources of raw materials has been put in place. An appeal for a fast track manufacture of hydroalcoholic gel/solutions was launched. A Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) procedure has been adopted in order to dispense off-label prescriptions of hydroxychloroquine and azithromycin combination. Focus groups were organized in order to set up therapeutic trials exploring possible strategies of COVID-19 treatment, such as serotherapy and BCG vaccine. This proactive and anticipatory policy has made it possible to meet the health challenges dictated by this crisis.

Lack of association between renin-angiotensin system (RAS) polymorphisms and hypertension in Tunisian type 2 diabetics.

BACKGROUND: The genes encoding renin-angiotensin system (RAS) components are potent candidate genes in both hypertension and diabetes namely ACE encoding the angiotensin converting enzyme and AGT encoding angiotensinogen. It has been suggested that the insertion/deletion (I/D) polymorphism in intron 16 of ACE gene is associated with ACE levels, and M235T gene polymorphism is associated with plasma AGT levels. AIM: We examined in this report the association between ACE I/D and AGT M235T polymorphisms with hypertension status in Tunisian type 2 diabetic subjects. METHODS: Thirty nine hypertensive and 22 normotensive type 2 diabetic Tunisian patients were recruited for this study. The I/D polymorphism of ACE gene was analysed with nested PCR in order to avoid mistyping heterozygous individuals and the M235T polymorphism of AGT gene was analysed using PCR and allele specific restriction. RESULTS: The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without hypertension (DD: 49%; ID: 41%; II: 10% vs DD: 36%; ID: 55%; II: 9%, respectively) (chi2=1.06, p=0.58). There was also no significant statistical difference between these two groups for the M235T polymorphism (TT: 20%; MT: 54%; MM: 26% vs TT: 27%; MT: 41%; MM: 32%, respectively) (chi2=0.95, p=0.62). CONCLUSION: RAS polymorphisms do not seem to play a role in the development of hypertension in the studied Tunisian type 2 diabetic subjects.

[Vitamins A, E and leptin in obese and non-insulin-dependent diabetes]. / Statut en vitamines a, e et léptinémie chez un groupe d'obèses diabétiques non insulino-dépendant.

BACKGROUND: At the obese ones, there is an imbalance between the free defenses antioxydants and radicals from where the installation of an oxydative stress, responsible for the development of non-insulin-dependent diabetes. AIM: Our objectives was to evaluate the levels of vitamins A, E and of leptin, to search the link witch could exist between vitamins and leptin. METHODOLOGY: We proportioned the rates in vitamins A, E and in leptine at 30 obese subjects diabetic of type 2 including 12 men and 18 women of average age (50.93 +/- 6.13) years not carrying pathologies other than the diabetes and obesity compared to 30 witnesses who theirs are paired according to the age and the sex.. RESULTS: Our results chows that levels of antioxidants did not differ between the two groups but we find a non significant decrease in vitamin E/(TC +TG) ratio (1.86 +/- 0.38 vs. 2.11 +/- 0.74 ; p = 0.08) and significant increase of vitamin A level in women obese with non-insulin-diabetes mellitus compared with control group of women (0.69 +/- 0.16 vs. 0.55 +/- 0.15 ; p = 0.01). Moreover a negative and significative correlation between vitamin E and leptin (r = 0.452 ; p = 0.01), and a negative and no significative correlation between vitamin A and leptin (2 = - 0.221; p > 0.05) were observed. CONCLUSION: The rate of vitamin A, is different for each sex with share. The vitamin E could have a negative control on the secretion of the leptin.

Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients.

OBJECTIVE: The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population. DESIGN: A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using a nested polymerase chain reaction amplification in order to identify correctly heterozygous individuals. RESULTS: The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without nephropathy (DD: 44%; ID: 46%; II: 10% vs. DD: 41%; ID: 47 %; II: 12%, respectively). There was also no significant statistical difference between the genotype distribution and allele frequencies of the (I/D) polymorphism in all type 2 diabetic subjects compared to non-diabetic controls with normal fasting blood glucose (DD: 43%; ID: 46%; II: 11% vs. DD: 37%; ID: 48%; II: 15%, respectively). CONCLUSIONS: In the present preliminary study, the (I/D) polymorphism within the ACE gene is likely not associated with diabetic nephropathy nor with type 2 diabetes in the Tunisian studied population.

Familial aggregation and excess maternal transmission of type 2 diabetes in Tunisia.

AIM: To evaluate the degree of familial aggregation of type 2 diabetes mellitus in Tunisia and to investigate transmission patterns of the disease and their relationships with patients' clinical profiles. METHODS: Family history of diabetes and clinical data were collected for 132 unrelated type 2 diabetic Tunisian patients. Diabetes status was recorded for first degree relatives (parents, siblings) and second degree relatives (aunts and uncles from both maternal and paternal sides). Information about family history of diabetes was gathered for a total of 1767 individuals. RESULTS: Familial aggregation of type 2 diabetes was prominent and more important among first degree relatives than among second degree relatives (p = 0.01). Among studied subjects, 70% reported at least one relative with diabetes and 34% had at least one parent with diabetes. Diabetes was more frequent among mothers than fathers of probands (p = 0.03). This maternal effect extends to second degree relatives as diabetes was more common among maternal than paternal aunts and uncles (p = 0.01). There is no significant difference in clinical and metabolic profiles between patients according to transmission patterns of the disease. CONCLUSION: These results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Tunisian studied population.

Food intake and high density lipoprotein cholesterol levels changes during ramadan fasting in healthy young subjects.

During the holy month of Ramadan, it is obligatory for all adult healthy Muslims to abstain from food, drink and smoking each day from dawn to sunset. The aims of our study were to evaluate the effects of Ramadan fasting on plasma lipids, lipoproteins and the change of food consumption in healthy subjects. Thirty young healthy and normal weighted adults (9 males and 21 females) were evaluated during three periods: 3 weeks before Ramadan (T0); the 4th week of Ramadan (T1) and 3 weeks after the end of Ramadan (T2). Main Clinical and biological parameters investigated were: body weight, blood glucose, plasma triglycerides (TG), plasma total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and. low density lipoprotein cholesterol (LDL-c) Body weight, and blood glucose were unchanged. There was a significant increase of the mean daily caloric intake, the lipids intake particularly mono-unsaturated and poly-unsaturated fatty acids (p < 0.001) and cholesterol intake (p < 0.001) during Ramadan with a decrease of the meal frequency. There was also a significant increase of plasma total cholesterol and HDL-cholesterol. The most striking finding was a significant increase in the HDL-Cholesterol during Ramadan +20% (p < 0.02). This increase was lost after Ramadan. Fasting Ramadan affects beneficially serum lipoprotein metabolism in young adult healthy subjects with an increase of HDL-cholesterol.

[Prevalence of anti-GAD autoantibodies in Tunisian children with type 1 diabetes]. / Prévalence des auto anticorps anti-GAD chez des enfants Tunisiens diabétiques de type 1.

The prevalence of GAD antibodies and its correlation with some autoimmune markers: ICA (islet cells antibodies), antinuclear antibodies, thyroid antithymune and antimicrosomes antibodies, were studied in 84 Tunisian type 1 diabetic children. The prevalence of GAD antibodies was 51.2% and decreased as a function of increasing duration of the disease. Their frequency was 84.6% in children with newly diagnosed diabetes (within 6 months of diagnosis) and only 29.41% in those with a longer duration of the diabetes (more than 5 years). ICA were present less frequently (21.4% of the children). 10.7% of the studied samples were positive with the two antibodies (GAD ab ICA), and 40% were positive only with GAD antibodies. We conclude that the GAD antibodies seems to be more associated to the development of type 1 diabetes than ICA. They are detected more frequently in patients with long standing disease, that's make their determination very interesting as diagnostic and predictive marker.