Use of Pentoxypline and Tocopherol in the treatment of Osteorradionecrosis: a literature review

Osteoradionecrosis (ORN) is a complication of radiotherapy (RT), which affects patients with head and neck cancer. Once established, an ORN does not disappear spontaneously and a standard treatment has not yet been defined. Treatment is often complex and multimodal. With a better understanding of the pathophysiology of ORN, new treatments and possibilities for the most predictable results of this difficult prognosis pathology arise. Under these circumstances, good results have been observed with an association of peripheral vasodilator drugs and antioxidants, such as pentoxifylline and tocopherol. The objective of this work was, through a review of the literature, to describe a pathophysiology of the ORN of the jaws and discuss as new perspectives of a conservative treatment with pentoxifylline and tocopherol. It was observed as an alternative to the drug association as a therapeutic alternative of the ORN, mainly in the early stages, it showed good results; However, it requires more controlled clinical studies to measure and consolidate the benefits that this treatment can provide patients.

Cerebral Insufficiency Caused by Diazoxide in a Premature Neonate with Congenital Hyperinsulinism

Diazoxide is a peripheral vasodilator that has been used for intravenous treatment of hypertensive emergencies. However, it is currently used mainly for hyperinsulinemic hypoglycemia in lower dose orally, and its major side effects are edema and pulmonary hypertension. Herein, we report the first association between periventricular leukomalacia (PVL) and intractable hypotension due to diazoxide. A Japanese female premature infant showed hypoglycemia concomitant with hyperinsulinemia. She was diagnosed with congenital hyperinsulinism, and oral diazoxide was started. Six days after starting diazoxide, she suddenly showed peripheral coldness, oliguria, and severe hypotension. The hypotension was refractory to general vasopressor therapies and persisted even after the discontinuation of diazoxide. Cranial echography showed periventricular echodensities followed by cystic PVL. Low-dose vasopressin effectively treated the hypotension. This single case reminds us the serious adverse events of diazoxide that have been forgotten, especially in premature neonates.

Comparative effects of nitric oxide dependent and independent vasodilation on impaired hindlimb revascularization in eNOS−/− mice

Ischemia due to vascular occlusion induces vasodilation as an initial response, followed by arteriogenesis or angiogenesis. Vasodilation through nitric oxide (NO) independent and dependent mechanisms may be sufficient to restore the altered neovascularization in pathological situations where the NO is altered. Using a posterior limb claudication model to evaluate ischemia-induced revascularization in eNOS−/− mice, we compared the effects of sodium nitrite, a NO-dependent vasodilator, and prazocin, an alpha-adrenergic blocker and NO-independent vasodilator, on hindlimb revascularization. We evaluated the blood flow of the hindlimbs, NO and nitrites metabolites, the expression of tissue endothelial cell markers and proangiogenic factors, as well as the gait locomotion. Our results suggest that the use of a peripheral vasodilator can substitute the initial absence of NO as an endogenous vasodilator. However, final resolution of the ischemic process requires a NO-mediated pathway, which through changes in vascular hemodynamics, promotes the generation of angiogenic messengers facilitating the functional recovery of the damaged limb.

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling

Although OPC-28326, 4-( N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice ( n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction.

Sympathetic nerve activity and peripheral vasodilator capacity in young and older men

Interindividual variability in sympathetic nerve activity (SNA) has provided insight into integrative mechanisms contributing to blood pressure (BP) regulation in humans. In young people, the influence of high SNA on BP is balanced by lower cardiac output and less adrenergic vasoconstrictor responsiveness. Older people have higher SNA and higher BP. We hypothesized that SNA has a restraining effect on peripheral vasodilator responsiveness in young and older men, such that individuals with higher tonic SNA would show less forearm vasodilatation to exogenous vasodilators. We measured muscle SNA (MSNA; microneurography) and forearm vasodilator responses to intra-arterial infusions of acetylcholine (ACh; endothelium dependent) and sodium nitroprusside (SNP; endothelium independent) in 13 young (age; 27 ± 1 yr) and 16 older (61 ± 2 yr) men. Forearm vascular conductance (FVC) responses to ACh were lower in the older men at the two highest doses (2 and 4 μg·100 ml−1·min−1; Δ395 ± 81 vs. 592 ± 87% and 412 ± 87 vs. 616 ± 132%, P < 0.05), and MSNA was higher (64 ± 4 vs. 41 ± 2 bursts/100 hb; P < 0.05). There was no difference in the FVC response to SNP between young and older men ( P > 0.05). In young men, there was an inverse relationship between resting MSNA and FVC responses (%change) to both ACh and SNP ( r = −0.83 and r = −0.83, respectively; P < 0.05). In older men, however, this relationship was not observed. Tonic SNA may act to restrain vasodilator responses in young men, whereas in older men a lack of such restraint may be protective against the pressor effects of higher SNA.

Sympathetic Neural Regulation of Blood Pressure: Influences of Sex and Aging

Sex and age have important influences on sympathetic neural control of blood pressure in humans. Young women are relatively protected against risk of hypertension due to greater peripheral vasodilator influences compared with young men and older people. This protective effect is lost at menopause. Older men and women have higher sympathetic nerve activity and tighter coupling between SNA and blood pressure, contributing to the increased risk of hypertension with aging.

The management of viper bites on the hand

The management of Viperidae snake bites of the hand is discussed from an assessment of the results of snake bite treatments in our clinic. Between 2010 and 2012, 23 patients presenting with venomous snake bites were admitted. None of the patients received a blood transfusion or underwent fasciotomy. There were no severe sensitivity reactions owing to the snake antivenom; however, one patient required a surgical procedure. Repetition of antivenom therapy is necessary to decrease the complication rate in patients with venomous snake bites. Moreover, the use of a peripheral vasodilator may decrease the complication rates in cases where the bite is on the digits.