Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti.

Aedes aegypti is the primary vector of a number of human pathogens including dengue virus (DENV) and Zika virus (ZIKV). Ae. aegypti acquires these viruses during the processing of bloodmeals obtained from an infected vertebrate host. Vertebrate blood contains a number of factors that have the potential to modify virus acquisition in the mosquito. Interestingly, low density lipopolyprotein (LDL) levels are decreased during severe DENV infection. Accordingly, we hypothesized that LDL is a modifiable factor that can influence flavivirus acquisition in the mosquito. We found that LDL is endocytosed by Ae. aegypti cells in a dynamin-dependent manner. LDL is also endocytosed by midgut epithelial cells and accumulates at the luminal midgut epithelium during bloodmeal digestion. Importantly, pretreatment with LDL, but not high density lipopolyprotein (HDL), significantly inhibited both DENV and ZIKV infection in vitro, and LDL inhibited ZIKV infection in vivo. This study identifies human LDL or 'bad cholesterol' as a modifiable factor that can inhibit flavivirus acquisition in Ae. aegypti. Identification of modifiable blood factors and critical cellular interactions that mediate pathogen acquisition may lead to novel strategies to disrupt the transmission cycle of vector-borne diseases.

Treatment of hypertension in diabetic patients.

Hypertension, common in diabetic patients, worsens not only the risk of cardiovascular complications, but also that of microangiopathic complications (nephropathy, retinopathy) of diabetes mellitus. It is thus important to ensure the perfect control of even mild hypertension in diabetic patients. However, treatment sometimes becomes difficult given that certain categories of antihypertensive drugs interfere with blood glucose control and/or lipid metabolism, interfere with the symptomatology of hypoglycemia, or promote orthostatic hypotension, a complication of autonomic neuropathy. A study was undertaken to determine the effects of rilmenidine, administered for 16 weeks, in 29 diabetic patients treated with insulin and experiencing mild-to-moderate hypertension (supine diastolic blood pressure, 96.7 +/- 0.5 mmHg). Administered as single-drug therapy, rilmenidine rapidly normalized blood pressure (systolic blood pressure, less than 160 mmHg; diastolic blood pressure, no more than 90 mmHg--supine) in 17 patients; this persisted throughout the trial period. Addition of a diuretic after 12 weeks in the remaining 12 patients led to normalization of blood pressure in nine additional patients. Blood glucose control (evaluated at home by weekly blood glucose measurements and by glycosylated hemoglobin levels) was unaffected by treatment. Plasma levels of cholesterol (total, high-density lipoprotein and low-density lipoprotein), triglycerides and proteinuria (or microalbuminuria) showed no change during the course of the trial. In conclusion, rilmenidine offers an effective and safe treatment for mild-to-moderate hypertension in diabetic patients treated with insulin and does not interfere with their blood glucose control.

Treatment of systemic hypertension in insulin-treated diabetes mellitus with rilmenidine.

The effects of a new alpha 2 agonist (S 3341 or rilmenidine) on blood pressure (BP), glycemic control, lipid metabolism and renal function were investigated during a 16-week open study in 29 insulin-treated diabetic patients with mild to moderate hypertension. There were 17 men and 12 women aged 50.9 +/- 2.2 years (mean +/- standard error of the mean). Duration of diabetes and insulin therapy was 218 +/- 24 and 143 +/- 30 months. After 2 weeks of placebo, systolic and diastolic BP was 165 +/- 3 and 97 +/- 0.5 mm Hg, respectively (supine). Rilmenidine (S 3341) given alone at daily doses of 1 or 2 mg according to the clinical response led to a prompt and sustained decrease of systolic and diastolic BP (159 +/- 4 and 88 +/- 1 mm Hg after 2 weeks; 149 +/- 3 and 85 +/- 1 mm Hg after 12 weeks; p less than 0.01). Seventeen patients (59%) had normal BP (systolic BP less than 160; diastolic BP less than 90 mm Hg, supine) after 12 weeks of S 3341. Diuretics were associated with S 3341 for the nonresponders at week 12; this led to normalization of BP in 90% of the patients at the end of the study. Glycemic control was assessed by home glucose monitoring (5 determinations/1 day per week), 24-hour glucosuria and postprandial plasma glucose at the outpatient clinic (n = 7) as well as by the measurement of the glycosylated hemoglobin. None of these parameters was significantly affected by S 3341.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary catecholamine excretion in patients with secondary adrenocortical insufficiency.

To evaluate the relationship between the secretion of cortisol and the activity of adrenal medulla in the secondary adrenocortical insufficiency, the excretion of epinephrine and norepinephrine was documented in 8 patients suffering from panhypopituitarism. Plasma levels and urinary excretion of cortisol were very low in baseline conditions, and the increase in these parameters of cortisol secretion occurring upon ACTH infusion was significantly reduced with respect to the response to ACTH documented in normal subjects. The mean value of urinary epinephrine excretion was at the lower limit of normal values, and a highly significant positive correlation was found between cortisolemia or cortisoluria and urinary epinephrine excretion in these patients. Despite a significant increase in cortisolemia and cortisoluria upon ACTH administration, this acute increase in adrenocortical activity was without any stimulatory effect on epinephrine or norepinephrine excretion. But, as in baseline conditions, a significant correlation was documented for the degree of adrenocortical activity and epinephrine excretion on the day of ACTH administration. It appears, therefore, that in severe secondary adrenocortical insufficiency the excretion of epinephrine is reduced proportionally to the decrease in adrenocortical activity.

Effect of the addition of simple sugars to mixed meals on the glycemic control of insulin treated diabetic patients.

In order to evaluate the long term effects of a daily intake of simple sugars upon the glycemic control, 10 insulin treated diabetic outpatients received, according to a randomized cross over design, a conventional or a sucrose-enriched isocaloric, isoglucidic diet (about 20 g sucrose per day, given as desserts and/or soft drinks during or after mixed meals) for 3 months each. The daily insulin doses remained identical during both diets: 0.58 +/- 0.07 vs 0.58 +/- 0.06 U/kg body weight (mean +/- SEM) after conventional and sugar-enriched diet, respectively. The percentages of short acting insulin were also similar: 50 +/- 4 vs 49 +/- 4%. The mean glycemic profiles after lunch and dinner were comparable with both regimens. Moreover, glycosylated hemoglobin levels were 10.0 +/- 0.3 vs 9.9 +/- 0.4% after conventional and sucrose enriched diet, respectively. Plasma cholesterol and triglycerides remained unchanged. In conclusion, a relatively small daily intake of sucrose for 3 months has no clinical and/or metabolic side effects. Therefore, it seems no longer justified to completely ban sucrose from the diet of diabetic patients.

Metabolic and psychological evolution of insulin dependent diabetic patients during a 6 months insulin-pen treatment.

The aim of the study is to assess whether an insulin pen-treatment (NovopenR) could be of interest in 10 type I insulin dependent diabetic patients (C-peptide: 0.04 +/- 0.01 pmol/ml, mean +/- SEM), with metabolic and psychological parameters being together taken into account. The daily insulin doses were comparable during the previous treatment with conventional syringes (2-3 daily injections of ActrapidR and MonotardR) and the pen therapy: 0.65 +/- 0.05 vs 0.68 +/- 0.04 U/kg b.w. The metabolic control assessed by HbA1 levels was unchanged before and after 6 months pen treatment: 10.7 +/- 0.7 vs 10.9 +/- 0.6%, respectively. However, fructosamine increased from 2.89 +/- 0.26 to 3.92 +/- 0.20 mmol/l (p less than 0.01) during pen treatment. The psychological objective variables showed no significant changes after pen treatment. In contrast, the staff ratings about the patients attitude toward illness and the spouse evaluation of subjective well-being increased from 40.2 +/- 8.4 to 49.5 +/- 7.8 (p = 0.03) and 34.8 +/- 23.4 to 51.1 +/- 21.1 (p = 0.04), respectively. In conclusion, in a limited group of patients, a multiple injection regimen by pen treatment did not lead to an improved metabolic control. However, subjective psychological tests showed that some aspects of well-being tended to improve.

Serum fructosamine level as a marker of glycemic control in diabetic patients with and without a residual C-peptide secretion.

Serum fructosamine was determined in 115 diabetic patients with a C-Peptide secretion (0.84 +/- 0.06 pmol/ml, mean +/- SEM) (Group A) and in 30 type I C-peptide negative totally insulin-dependent subjects (less than 0.05 pmol/ml) (Group B). A significant correlation between fructosamine and HbA1 values (r = 0.70, p less than 0.001) was evidenced in Group A. In contrast, such a correlation was not found in Group B (r = 0.33, p greater than 0.05). Fructosamine levels were also in good agreement with the physician's ratings of the degree of glycemic control in Group A, but not in Group B. It is concluded that the fructosamine measurement represents a complement rather than an alternative to HbA1, in particular in unstable diabetic patients.