Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection.

In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1ß, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response.

Resiniferatoxin lowers TNF-α, NO and PGE2 in the intestinal phase and the parasite burden in the muscular phase of Trichinella spiralis infection.

During the course of infection with Trichinella spiralis, an inflammatory response is triggered at the intestinal level in the host, playing a crucial role in the expulsion and elimination of the parasite. However, several studies have demonstrated that this inflammatory response is harmful to the host; hence, the importance of studying molecules with therapeutic potential like resiniferatoxin, which is known to have an anti-inflammatory effect both in vitro and in vivo. In this article, we evaluated the anti-inflammatory activity of resiniferatoxin during the intestinal phase of T. spiralis infection by quantitatively determining the levels of TNF-α, NO and PGE2 as well as the percentage of eosinophils in the blood and intestinal pathology. In addition, parasite burden was determined during the muscle infection. Our results show that resiniferatoxin lowered the serum levels of TNF-α, NO and PGE2 , as well as the percentage of eosinophils in the blood and intestinal pathology during the intestinal infection. Moreover, resiniferatoxin also lowered the parasite burden in muscle, resulting in a reduction of the humoral response (IgG) associated to treatment with resiniferatoxin. These findings suggest a potential therapeutic use of the anti-inflammatory effect of resiniferatoxin, which also contributes to host defence against the challenge of T. spiralis infection.

Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.

BACKGROUND: The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations. METHODS: Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort. RESULTS: Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P<0.001). Subjects with homocysteine in the upper quartile (≥ 18 µmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 µmol/L), in both populations (P<0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate. CONCLUSIONS: This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations.

[Distal sensorimotor polyneuropathy in type-2 diabetes]. / Polineuropatía sensitivomotora distal en la diabetes tipo II.

OBJECTIVE: The objective of the study was to relate the symptoms attributed to motor-sensitive diabetic polyneuropathy to the findings in the exploration of osteo-tendinous reflexes and vibrative sensibility. DESIGN: We carried out an observation prospective study of a crossover type, where the method of selection was simple random. SETTING: The study was performed in the Carranque Health Centre, Málaga. PATIENTS: The sample consisted of those patients with type II Diabetes and over 40 when first recorded, who were seen by one of five general medical practices over a one-year period. There were 120 in all. MEASUREMENTS AND MAIN RESULTS: Average age was 65.7 (SD = 9.5). There were 47 men and 73 women. Paraesthesia was reported in 40 cases (33.3%), muscular spasms in 41 (34.1%) and pain in 31 (25.8%). The findings were: lack of Achilles reflex in 65 cases (54.1%) and vibrative anaesthesia in 55 cases (45.8%). Lack of Achilles reflex showed a statistically significant association with nocturnal muscular spasms (p = 0.04) and vibrative anaesthesia (p = 0.001). Vibrative anaesthesia showed a prevalence which was directly proportional to age (p = 0.0003). CONCLUSIONS: We concluded that lack of Achilles reflex and vibrative anaesthesia in diabetic patients are good indicators of the existence of motor-sensitive Polyneuropathy, although vibrative anaesthesia was found to be related to other factors such as age.