Comparative analysis of changes in rats organisms exposed to microgravity and head-down suspension

Comparative analysis of metabolic and structural shifts in rats following 14 days of microgravity aboard biosatellite Cosmos-2044 and their tail-suspended synchronous controls gave evidence that suspension-induced deprivation of hind limbs of support loading yields inherent to microgravity shifts the endocrine control of energy, plastic, and mineral metabolism. The conclusion has been drawn that tail-suspension can be used as a model of the microgravity effects on the musculoskeletal apparatus and the endocrine systems controlling metabolism in muscles and bones.     

Pharmacokinetic features, immunogenicity, and toxicity of B43(anti-CD19)-pokeweed antiviral protein immunotoxin in cynomolgus monkeys

Withdrawal responses to mechanical and thermal stimuli applied to the plantar surface of the hindpaw were measured before and after bone damage. In separate groups of rats the bone was injured by scraping the periosteum of the tibia, drilling a hole through the tibia, aspirating bone marrow, or drilling a hole through the calcaneus. Scraping the periosteum did not alter withdrawal responses to the mechanical stimuli, or evoke nocifensive behavior. In contrast, secondary mechanical hyperalgesia and allodynia, and cold allodynia were observed after a hole was drilled through the tibia or calcaneus and after aspiration of bone marrow. The secondary hyperalgesia peaked at 2 h after injury. Drilling a hole through the calcaneus permitted primary hyperalgesia to be easily quantified. Primary hyperalgesia lasted up to 24 h after injury. Nocifensive behavior characterized by a lifting and guarding of the damaged limb was also observed after a hole was drilled through the tibia or calcaneus. Drilling a hole through the tibia or calcaneus should be a useful experimental model for investigating the mechanisms underlying bone pain.     

The Notch signalling pathway in hair growth

The Notch signalling pathway is an important mediator of cell fate selection whose involvement in epidermal appendage formation is now becoming recognised. Hair follicle development and hair formation involve the co-ordinated differentiation of several different cell types in which Notch appears to have a role. We report intricate expression patterns for the Notch-1 receptor and three ligands, Delta-1, Jagged-1 and Jagged-2 in the hair follicle. Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1 is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode. Expression of Jagged-1 or Jagged-2 overlaps Notch-1 expression at all stages. In mature follicles, Jagged-1 and Jagged-2 are expressed in complementary patterns in the follicle bulb and outer root sheath, Jagged-1 in suprabasal cells and Jagged-2 predominantly in basal cells. In the follicle bulb, Jagged-2 is localised to the inner (basal) bulb cells next to the dermal papilla which do not express Notch-1, whereas Jagged-1 expression in the upper follicle bulb overlaps Notch-1 expression and correlates with bulb cell differentiation into hair shaft cortical and cuticle keratinocytes.     

Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro

The GER human pancreatic carcinoma cell line possesses receptors for 1,25-dihydroxyvitamin D3. We report that the vitamin D analogue EB 1089 inhibits the growth of these cells in vitro and when grown as tumour xenografts in immunodeficient mice. Tumour-bearing mice were given EB 1089 at a dose of 5 microg kg(-1) body weight i.p. thrice weekly for 4-6 weeks. Tumour growth was significantly inhibited in treated animals compared with controls in the absence of hypercalcaemia. These findings may have therapeutic implications in pancreatic cancer.     

Heart reduction surgery: an analysis of the impact on cardiac function

OBJECTIVES: Reports of improved ejection fraction, coupled with decreased filling pressures, have prompted a number of centers to begin evaluating the efficacy of heart reduction surgery to ameliorate symptoms of heart failure. However, the impact of this operation on cardiac mechanics is unknown. We applied a multiple compartment elastance model to simulate the effects of excising cardiac mass on heart function. METHODS: The left ventricle was divided into two functional compartments to simulate excision of part of the wall. At multiple increments of mass reduction, the resulting end-systolic elastance, ejection fraction, stroke volume, end-diastolic pressure and volume, and diastolic stiffness were determined. RESULTS: Changes in systolic function were accompanied by offsetting changes in diastolic function; consequently, overall pump function (the Frank-Starling Relationship) was found to be depressed. The geometric rearrangement associated with this operation leads to a reduction in wall stress for a given level of pressure generation, thus implying an increase in the efficiency with which wall stress is transduced into intraventricular pressure. CONCLUSIONS: Overall pump function is depressed in the short run after heart reduction surgery. However, on the basis of theoretic arguments, heart reduction surgery may have long-term beneficial implications. Importantly, this analysis revealed that changes in parameters of ventricular function have different implications during heart reduction surgery than when such changes are observed with inotropism caused by acute pharmacologic therapy.     

Primary cerebral lymphoma in Zimbabwe: a report of three patients

Primary central nervous system lymphoma (PCNSL) is steadily increasing. Immunosuppressed individuals are at particular risk. In AIDS patients a clinical diagnosis of PCNSL is made in 0.5 to 8.4%, and a post mortem diagnosis in up to 11% of cases. In spite of the extensive HIV epidemic in parts of Africa, a literature search revealed only one African report of this condition. The reasons for this apparent infrequency are not clear. Possibilities include under diagnosis or early demise of patients due to other AIDS related illnesses of earlier onset. Three patients with primary cerebral lymphoma from Zimbabwe are presented. All were young, with tumours of high grade showing typical features.     

Infective endocarditis prophylaxis in children

There has been no significant decrease in the incidence of infective endocarditis. Contributing factors include increased survival of susceptible patients, increased number of 'at risk' procedures and poor compliance with existing recommendations. This review highlights the scientific basis for prophylaxis, identifies patients and procedures at risk, and tabulates a simple protocol.     

Maternal nutritional status, diabetes and risk of macrosomia among Native Canadian women

Using cloned kDNA sequences from the reference strain of Leishmania tropica IC-067, we have screened leishmanial isolates from Laikipia District of Kenya and identified these isolates as L. tropica. One isolate, IC-331, from a rat (Rattus rattus) was typed as L. tropica. This is the first time that L. tropica has been isolated from a wild rodent in Kenya and thus the first indication that the disease caused by L. tropica might be a zoonosis. The leishmanial isolates, especially those of sandflies, display extensive heterogeneity, prompting a need for selecting local and/or regional reference strains to generate species-specific DNA probes for use in identifying field isolates.     

Microanalysis of lung airway surface fluid by capillary electrophoresis with conductivity detection

The thin layer of fluid that covers the surface of the epithelia lining the conducting airways plays an important role in primary pulmonary defense, and its composition may be a critical factor in the pathogenesis of several lung diseases including cystic fibrosis. Despite its physiological importance, the composition of airway surface fluid (ASF) is poorly understood due to considerable difficulties in sample collection from the 5-30 microns thick layer and subsequent analysis. We have used a novel technique for sample collection and microanalysis of ASF (nanoliter sample required) by capillary electrophoresis with conductivity detection. Limitations on the diameters of capillary required for the sample injection process and for the conductivity detector require the use of coupled separation capillaries with different external diameters. Two different methods were used to construct a butt-joint coupling for capillaries of different outer diameters. Reasonable efficiency is observed with the coupled capillaries (N = 100000 plates m-1) compared to an unbroken single capillary (N = 180000 plates m-1). The use of conductivity detection allows greater flexibility in method development and the possibility of determining a greater variety of ions than with a previous indirect-UV method. In the present study, we describe the analysis of cations (Na+, K+, Ca2+, Mg2+) and anions (Cl-, NO2-, NO3-, SO4(2-), PO4(2-), HCO3-) in rat ASF. Particular attention was paid to developing washing procedures which limited fouling of the conductivity sensor. In healthy rats, ASF was found to be hypotonic compared to plasma levels, consistent with some observations made in human airways.