Effects of long-term high-altitude hypoxia on isolated fetal ovine coronary arteries

OBJECTIVE:To examine the effects of long-term high-altitude hypoxia on the contractile properties of isolated fetal coronary arteries. METHODS: Maximal contractile responses (T(max)) to 90 mmol/L KCl and the thromboxane A(2) mimetic U46619 were measured in proximal (PLCx) and distal left circumflex (DLCx), left anterior descending (LAD), and right coronary arterial (RCA) rings from high-altitude and control fetuses. Paired studies were conducted with and without nitric oxide synthase (NOS) inhibitors, Nomega-nitro-L-arginine and Nomega-nitro-L-arginine ester. RESULTS: In high-altitude fetuses, 90 mmol/L KCl T(max) responses in both intact and NOS-blocked rings decreased by approximately 62% in PLCx, approximately 59% in DLCx, approximately 57% in LAD, and approximately 47% in RCA (n = 9-18/group; P <.05). High-altitude vessels also exhibited decreased sensitivity to U46619. NOS blockade potentiated T(max) to U46619 in the high-altitude RCA segments and augmented T(max) to U46619 in high-altitude RCA compared with its treated control counterpart (P <. 05). CONCLUSION: These results suggest that nitric oxide influences the pharmacologic responsiveness of the RCA to U46619. Furthermore, long-term high-altitude hypoxia significantly alters the contractile capabilities of fetal coronary arteries. These observations may partially explain the maintained redistribution of cardiac output to the fetal heart during exposure to long-term high-altitude hypoxia.     

Effects of organophosphorus pesticides and their ozonation byproducts on gap junctional intercellular communication in rat liver cell line.

The effects of organophosphorus pesticides (OPs), oxons and their ozonation byproducts on gap junctional intercellular communication (GJIC) on cultured BRL cell line were investigated using scrape loading and dye transfer (SL/DT) technique. The neutral red uptake assay was used to identify the non-cytotoxic levels of diazinon, parathion and methyl-parathion applied to GJIC assay. The concentration-dependent inhibition of GJIC was observed over a range of 50-350 mg/l diazinon, parathion and methyl-parathion after 90 min incubation compared with the vehicle control. However, oxons and ozonation byproducts of OPs had no inhibition effect on GJIC at any of the concentrations tested. The inhibition of GJIC by OPs was reversible after removal of the tested pesticides followed by incubation with fresh medium. The present study suggested that the ozonation treatment could be used for the detoxification of drinking water and food crops contaminated with diazinon, parathion and methyl-parathion without formation of GJIC toxicity.     

Pharmacologic and Pharmacokinetic Assessment of Anti-TGFβ2 Aptamers in Rabbit Plasma and Aqueous Humor

Purpose The aim of the study is to determine the bioactivity and effects of PEGylation on the pharmacokinetics in rabbit aqueous humor and plasma of an aptamer directed against TGFβ2. Methods Pharmacological activity of anti-TGFβ2 aptamer in rabbit ocular fluid was demonstrated using a mink lung epithelial cell proliferation assay. For pharmacokinetic analyses, concentrations of aptamers in plasma and aqueous humor were determined over time following bilateral subconjunctival administration to Dutch-belted rabbits using a hybridization-based pseudo-enzyme-linked immunosorbent assay (ELISA) assay. Results Anti-TGFβ2 aptamer (ARC81) binds to human TGFβ2 with a K_D of approximately 5 nM and inhibits the activity of human TGFβ2 in vitro in a cell-based assay with an IC₅₀ of approximately 100 nM. ARC81 blocks endogenously derived TGFβ2 in rabbit aqueous humor in vitro with an IC₅₀ of approximately 200 nM and an IC₉₀ of approximately 1 μM. In vivo in rabbit, ARC81 [no polyethylene glycol (PEG)] entered systemic circulation rapidly (t_max = 1 h in plasma) relative to aptamer conjugates ARC117 (20 kDa PEG) and ARC119 (40 kDa PEG), which showed prolonged residence in the subconjunctival space and aqueous compartment (t_max = 6 and 12 h, respectively, in plasma). Both 20- and 40-kDa aptamer conjugates reached maximal concentrations (C_max) in aqueous humor of 23–30 nM and remained at or above 1 nM for as long as 12 h. Conclusions Pharmacologically active levels of anti-TGFβ2 aptamers can be sustained in the ocular fluid and local tissue environment over a 12-h period after single administration. Daily subconjunctival administration of PEGylated anti-TGFβ2 aptamers should allow further pharmacological evaluation of these agents in a rabbit conjunctival scarring model. Perioperative administration, via subconjunctival injection, may prove to be an effective means to deliver therapeutic quantities of TGFβ2 aptamer conjugates in trabeculectomy procedures.     

CANINE DISTEMPER IN THE RHESUS MONKEY (MACACA MULATTA)

Canine distemper has been transmitted to rhesus monkeys by a variety of methods. The disease is strikingly similar if not identical in its features with distemper in dogs.     

THE LESIONS IN THE SKELETAL MUSCLES IN EXPERIMENTAL SCORBUTUS

1. Muscle degeneration was constantly found in the intercostal muscles of scorbutic guinea pigs. 2. It has likewise been found in the masseter and diaphragmatic muscles. 3. Exercise will produce an identical lesion in other skeletal muscles in scorbutic animals. 4. The lesions appear to be an intrinsic part of the scorbutic process. 5. It is suggested that the tenderness over muscles in scorbutic animals and in man may be due to this myopathy.     

Pediatrics: Benefits of Hospitalizing Mother with Child

The use of hospitalists—physicians who limit their practice largely or exclusively to hospital inpatient care—has been a growing trend in the United States. The authors examine some pressures affecting an academic medical center and present the results of a hospitalist pilot project there. Based on the criteria of reduced patient length of hospital stay, hospital financial savings, physician satisfaction, and payer interest, the pilot hospitalist program was successful within 6 months.