The role of oxidative products of nitrous oxide and the tumor necrosis factor alpha in dilated cardiomyopathy

Dilated Cardiomyopathy (DCM) is a disease of the myocardium and one of the leading causes of death in patients with heart diseases. We explored the role of increased Nitric oxide and TNF-alpha on the pathogenesis and progression of DCM. 25 patients with DCM, and 20 apparently healthy age and sex matched controls, were studied. Patients were divided into 2 groups according to the presence or absence of pulmonary hypertension. All patients and controls were subjected to full cardiological assessment including plain chest x-ray, 12 lead ECG, and thorough 2D and Doppler echocardiography study. Laboratory investigations included measurement of plasma nitrite, nitrate and TNF-alpha levels. Plasma nitrite, nitrate and TNF-alpha concentrations were significantly elevated in DCM patients as compared to controls, and the elevation correlated with the decreasing functional status of the patients. It is concluded that plasma nitrite, nitrate, and TNF-alpha levels in DCM are not only linked to the severity of heart failure at presentation and during follow up, but also to the worsening of left ventricular function as evidenced by the decrease in ejection fraction and increase in end systolic and diastolic ventricular diameters during the echocardiography evaluation.     

A randomized clinical trial comparing single- and multi-dose combination therapy with diethylcarbamazine and albendazole for treatment of bancroftian filariasis

The Global Program for Elimination of Lymphatic Filariasis calls for mass drug administration for endemic populations outside of sub-Saharan Africa with a single dose of diethylcarbamazine (DEC) and albendazole (Alb) annually for 4-6 years. Single-dose DEC/Alb dramatically reduces blood microfilaria (MF) counts, but most treated subjects fail to completely clear MF after a single dose. A more effective regimen might reduce the number of years required for elimination programs. We performed a randomized clinical trial in Egyptian adults with asymptomatic microfilaremia to compare treatment with seven daily doses of oral DEC (6 mg/kg) and Alb (400 mg) with a single dose of the same combination. We also studied the effect of re-treatment with single-dose DEC/Alb 12 months after the first treatment course. Multi-dose DEC/Alb was significantly more effective than single-dose therapy for reducing and clearing microfilaremia (mean reduction in MF/ml relative to pretreatment counts at 12 months, 99.6% versus 85.7%, with complete clearance in 75% versus 23.1%). The two regimens had similar activity against adult filarial worms, as indicated by serial ultrasound assessments. Neither regimen resulted in complete clearance of filarial antigenemia. There was no difference in adverse events, which were mild to moderate. Blood microfilaria and parasite antigen clearance rates increased following re-treatment. Multi-dose DEC/Alb may be a useful option for filariasis elimination programs, especially in the first year (when enthusiasm for mass drug administration and coverage rates are high), to quickly reduce community MF loads and transmission rates.     

Vascular inflammation and endothelial dysfunction in fracture healing

Angiogenesis is an important step in bone fracture healing. In this article, we report on the healing of long bone fractures, and the involvement of the vascular and the inflammatory systems in the process. We conducted a prospective study of 20 healthy adults with traumatic long bone fracture. One week after fracture, and then 1 month later, we evaluated markers of inflammation: vascular responsiveness (brachial endothelial function and ankle brachial index) and inflammatory and cytokine levels osteopontin [OPN], E-selectin, and vascular endothelial growth factor [VEGF]). Long bone fractures caused intense vascular and inflammatory responses, represented by high levels of OPN, Eselectin, and VEGF. In vivo measurements demonstrated severe endothelial dysfunction, which could support the idea that the vascular system is recruited to build new blood vessels that support bone regeneration.     

Immunoglobulin levels, opsonic activity and phagocytic power in Egyptian thalassemic children

Serum IgG, IgM and IgA were determined in 25 patients with homozygous beta thalassemia and 7 with the trait. The levels were increased in homozygous patients and increased further after splenectomy. Serum opsonic activity against Salmonella typhi and staphylococci was impaired in homozygous patients. Splenectomy caused more impairment against salmonella only. Similarly, phagocytic power against both organisms was lower in beta thalassemia. Further decrease against salmonella occurred after splenectomy. Patients with thalassemia trait did not differ from normal controls.     

The influence of fasting on the susceptibility of mice to hepatotoxic injury

The hepatotoxic effects of eight compounds as determined by serum activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and sorbitol dehydrogenase (SDH) were investigated in normally fed mice on the one hand and 24-hr-fasted mice on the other. Fasting strongly enhanced serum-enzyme elevations induced by carbon tetrachloride, paracetamol, thioacetamide, and bromobenzene. The hepatotoxic effects of phalloidin and allyl alcohol were only moderately increased by fasting and those of α-amanitin and praseodymium not at all. The fasting-induced aggravation of CCl₄ hepatotoxicity (evidenced also by histological findings) appeared already after 12 hr and was maximal after 24 hr of food deprivation. Fasting for 24 hr decreased the liver weight by 29%, hepatic glycogen by 93%, and hepatic glutathione (GSH) by 50% but increased liver triglycerides by 162%. Aniline hydroxylase and aminopyrine N-demethylase activities were higher in the liver homogenate supernatants from fasted than from fed mice but microsomal protein content as well as microsomal NADPH-cytochrome c-reductase activity remained unchanged and microsomal cytochrome P-450 content even decreased upon fasting. Fasting did not influence the in vitro irreversible binding of ¹⁴CCl₄ and [³H]paracetamol to hepatic microsomal proteins nor the in vivo binding to hepatic proteins of [³H]paracetamol. It enhanced, however, the total concentration of ¹⁴CCl₄ in the liver by 30% and produced a trend toward higher values in the extent of ¹⁴CCl₄ bound in vivo to hepatic protein. Spontaneous and CCl₄-induced lipid peroxidation were the same in hepatic microsomes from fed and fasted mice. No unique explanation can be made for the increased susceptibility of mouse liver to toxic injury induced by fasting. Several factors must be considered: depletion of both hepatic glycogen and glutathione as well as hepatic lipid accumulation. Overnight fasting of mice (and of other small animals presumably too) may change the results of toxicological experiments to an unpredictable degree and should thus be avoided.     

The development of USP botanical dietary supplement monographs, 1995-2005

The development of USP botanical dietary supplement monographs by the Subcommittee on Natural Products (1995-2000) and the Dietary Supplements-Botanicals Committee of Experts (2000-2005) of the USP is described in this review. Featured details include the USP as an organization, focusing upon its history, mission, and publication of the United States Pharmacopeia-National Formulary (USP-NF); the formulation and composition of botanical dietary supplement monographs and related general chapters, as well as appropriate admission criteria; and a summary of the accomplishments of the Committees (1995-2005).