Reversible Cerebral vasoconstriction syndrome associated with the use of sibutramine

The reversible cerebral vasoconstriction syndrome, also known as Call-Fleming syndrome, was initially described in 1988, and is characterized by a clinical syndrome of headaches episodes, generally the “thunderclap” pattern, due to a deregulation of the vascular tonus, leading to segmentary cerebral vasoconstriction and secondary neurological deficits, including those by ischemic or hemorrhagic stroke. In this paper, we present two illustrative cases of this syndrome due to the use of sibutramine. To our knowledge, this situation hasn’t been described as related drug before.

Ethyl Acetate Fraction and Isolated Phenolics Derivatives from Mandevilla moricandiana Identified by UHPLC-DAD-ESI-MSn with Pharmacological Potential for the Improvement of Obesity-Induced Endothelial Dysfunction

Endothelial dysfunction in obesity plays a key role in the development of cardiovascular diseases, and it is characterized by increased vascular tonus and oxidative stress. Thus, this study aimed to investigate the vasodilatory and antioxidant activities of Mandevilla moricandiana ethyl acetate fraction and subfractions. Vascular effects were investigated on aorta isolated from control and monosodium glutamate (MSG) induced-obese Wistar rats, and antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods. The ethyl acetate fraction (MMEAF) induced a concentration-dependent vasodilation on aortic rings through the NO pathway, with the involvement of histamine H1 and estrogen ERα receptors and showed potent antioxidant activity. In aorta of MSG obese rats, maximal relaxation to acetylcholine was increased in the presence of MMEAF (3 µg / mL), indicating that MMEAF ameliorated obesity-induced endothelial dysfunction. Quercetin and kaempferol aglycones and their correspondent glycosides, as well as caffeoylquinic acid derivatives, A-type procyanidin trimer, ursolic and oleanolic triterpenoid acids were identified in subfractions from MMEAF and seem to be the metabolites responsible for the vascular and antioxidant activities of this fraction.

Hypertension as Three Systematic Dysregulations of Na+ Homeostasis in Terrestrial Mammal, and Salt in Gut Might Cause Brain Inflammation

Although Na+ homeostasis in vivo is essential for mammals, it is known that excessive salt (NaCl) intake has played a major role in the development of hypertension. In vivo, there is a hormonal system, the renin-angiotensin-aldosterone system (RAAS), that specializes in regulating Na+ retention, especially the amount of Na+ in plasma. Na+ homeostasis in vivo has been achieved mainly by the RAAS, through regulation of vascular tonus (blood pressure) and Na+ handling in the kidney (Na+ diuresis). Recent studies have revealed a third mechanism of Na+ homeostasis in vivo: regulation of interstitial Na+ levels in tissues, such as subcutaneous tissues, by tissue macrophage immunity. In the pathogenesis of salt-sensitive hypertension, Recent research have been revealed that three molecular axes (Ang II - Rho/NOX-eNOS system, Aldosterone-rac1 -ENaC system, and tissue Na+ − TonEBP in macrophage -VEGF-c) are significantly involved in maintaining Na+ homeostasis in salt induced hypertension. Furthermore, the mechanism by which salt causes hypertension via the immune system (intestinal, local mucosal, and tissue immunity) has also been reported. In this article, we would like to propose that three molecular dysfunctions are involved in the development of salt-sensitive hypertension through three immunological mechanisms in the maintenance of Na+ homeostasis. Next, I would like to explain the importance of gut-RAAS and abnormality of intestinal microflora (dysbiosis) in salt-sensitive hypertension. It has been known that the metabolites (e.g., short-chain fatty acid neural amino) produced by microflora are deeply involved in central (CNS) and sympathetic nervous system (SNS) activity. In addition, we would like to explain of the importance of brain-RAAS and cerebral inflammation in salt-sensitive hypertension. Moreover, recent research have revealed that the detection-mechanism in the brain for Na+ concentration([Na+]) in vivo and in the tongue for [Na+] in diet. These finding suggests that excessive salt intake may cause brain dysfunction, most delicate organ, before the onset of salt sensitive hypertension, and may also destroy brain structure after the onset of salt sensitive hypertension. Thus, we would like to insist that excessive salt intake might not only induce hypertension, but also be toxic especially for brain. Finally, we would like to explain that The DASH diet (Dietary Approaches to Stop Hypertension) is one of the universal diets for adult human, not only by reducing salt, but also by reducing metabolic stress and improving of dysbiosis.

Enhanced sympathetic neurotransduction in the superior mesenteric artery in a rat model of heart failure: role of noradrenaline and ATP.

Heart failure (HF) is associated with neurohumoral activation, which in turn leads to an increased peripheral resistance. In mesenteric vasculature, perivascular innervation plays relevant role maintaining vascular tonus and resistance. Therefore, we aimed to determine the possible alterations in superior mesenteric artery (SMA) perivascular innervation function in HF rats. HF was induced by coronary artery occlusion in male Wistar rats, and sham-operated (SO) rats were used as controls. After 12 weeks, a greater vasoconstrictor response to electrical field stimulation (EFS) was observed in endothelium-intact and -denuded SMA of HF rats. Alpha-adrenoceptor antagonist phentolamine diminished this response in a higher magnitude in HF than in SO animals. However, the noradrenaline (NA) reuptake inhibitor desipramine increased EFS-induced vasoconstriction more in segments from HF rats. Besides, EFS-induced NA release was greater in HF animals, due to a higher tyrosine hydroxylase expression and activity. P2 purinoceptor antagonist suramin reduced EFS-induced vasoconstriction only in segments from SO rats, and ATP release was lower in HF than in SO. Moreover, nitric oxide (NO) synthase inhibitor L-NAME enhanced EFS-induced vasoconstriction in a similar extent in both groups. HF was not associated with changes in EFS-induced NO release or the vasodilator response to NO donor sodium nitroprusside. In conclusion, HF post myocardial infarction enhanced noradrenergic function and diminished purinergic co-transmission in SMA and did not change nitrergic innervation. The net effect was an increased sympathetic participation on the EFS-induced vasoconstriction, that could help to understand the neurotransduction involved on the control of vascular tonus in HF.

Relationship between effects of riociguat and levels of methemoglobin in patients with chronic thromboembolic pulmonary hypertension

Background Soluble guanyl cyclase (sGC) is a receptor for nitric oxide (NO) and plays an important role in vascular tonus. sGC stimulant is a therapeutic agent for pulmonary hypertension and an advantage of sGC stimulant over phosphodiesterase (PDE)-5 inhibitors is that sGC stimulant exerts its effect even when NO production is reduced. NO derived from vascular endothelial cells is immediately absorbed by hemoglobin (Hb), which leads to the production of methemoglobin (Met-Hb) when oxidized. Previous report has shown that the therapeutic effect of PDE-5 inhibitors was associated with levels of Met-Hb. Purpose In this study, we examined the relationship between the effect of riociguat and levels of Met-Hb in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods The study population comprised 18 patients with CTEPH. Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were assessed before and after administration of riociguat, and changes in mPAP and PVR were defined as ΔmPAP and ΔPVR, respectively. Since the level of Met-Hb was obtained as the percentage of Hb (FMet-Hb), the amount of Met-Hb was calculated by following formula: Met-Hb (mg/dL) = Hb (g/dL) × FMet-Hb (%) × 10. Results The amount of Met-Hb value before administration of riociguat was significantly correlated with the degree of improvement in mPAP and PVR after administration of riocigat (R=−0.502, P<0.05 mPAP; R=−0.481, P<0.05 PVR, respectively) as shown in figures. Conclusion Our findings suggest that the level of Met-Hb before treatment may predict the therapeutic effect of sGC stimulants in patients with CTEPH. Funding Acknowledgement Type of funding source: None

Role of physiotherapeutic factors in improving peripheral hemodynamics in patients with rheumatoid arthritis

130 rheumatoid arthritiS patients (RA pts) were distributed in the comparative groups on the basis of used physiotherapy methods and placebo‑physiotherapy. Violation of peripheral blood‑flow mainly vessels of small and medium caliber mainly vessels of small and medium caliber in RA pts in comparison with group of practically healthy persons at baseline was detected, the severity of these abnormalities depended on duration of disease. The comparative analysis of basic rheovasographic indexes in RA pts before and after treatment in parallel groups treated with electrosleep‑therapy, low‑frequency magnetotherapy, bioresonant stimulation and placebo‑physiotherapy was conducted. Significant differences in studied indexes after completed course of treatment such as diminishing of asymmetry of blood‑filling in extremities at all types of physiotherapy, increasing of pulse vascular blood‑filling of extremities after electrosleep‑therapy and bioresonant stimulation, decrease of vascular tonus after application of low‑frequency magnetotherapy were defined. Course of placebo‑physiotherapy has not demonstrated statistically meaningful changes in rheovasographic indexes. Clinically significant adverse events during physiotherapy treatment were not detected. Conclusion: including of physiotherapy in the management of RA pts in term to improve peripheral hemodynamics and to prevent vascular complications can be recommended.

Colloid osmotic pressure during and after surgical interventions in adult and geriatric dogs

ABSTRACT: The objective this study is to evaluate colloid osmotic pressure (COP) fluctuations in adult and senile dogs during surgical interventions. Thirty-six healthy dogs to surgical interventions, distributed in two groups, A and B, according to their age, and were all subjected to the same anesthetic protocol. Values of albumin, total plasmatic protein and COP were evaluated from samples collected before pre-anesthetic medication, fifteen minutes after pre-anesthetic medication, and shortly after the end of the intervention. Results were tested using t-test to compare among groups and ANOVA for repeated measures followed by Tukey’s test to compare different moments within the same group. Statistical significance was set at p<0.05. In both groups, significant decreases were observed in colloid osmotic pressure, as well as albumin and total proteins (p<0.001). Despite slightly lower COP values for the group of adult animals, this difference was not significant as there was a high individual variation within groups. The results therefore indicate no difference in colloid osmotic pressure values or fluctuation patterns among adult and senile dogs (p=0.124). The observed results indicate that colloid osmotic pressure decreases significantly during surgical procedures, due to hypotension caused by the anesthetic drugs and to hemodilution caused by the fluid administration but there is no difference between groups. However, in both adult and senile dogs, these variables recover gradually after the animals awaken, through increased urine production and recovery of vascular tonus, indicating the successful reestablishment of homeostasis.