Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations

The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.     

Mid-infrared spectroscopy on skin using a silver halide fibre probe in vivo

Background/aim: Mid-infrared spectroscopy is a versatile method for in vivo investigation of skin after topical treatment with skin care products.
Methods: FTIR-spectrometer (Bruker Optics) with a flexible silver halide fibre probe (Infrared Fiber Sensors).
Results: Absorbance spectra from 700 to 3000 cm⁻¹ have been recorded to gain information about proteins (amide-I and amide-II vibrations at 1650 and 1550 cm⁻¹), esters (1740 cm⁻¹), carboxylic acid (1710 cm⁻¹), polyalcohols (1050 cm⁻¹) and hydrocarbons (CH _n vibrations at 2800–3000 cm⁻¹).
Conclusions: Using the particular light guide, we were able to measure for the first time the effects of lip care products on lips directly. Furthermore, water binding and glycerol content of the skin could be determined simultaneously, as well as the replenishment of lipids by lipid-enriched bath oil.     

Effects of probucol on renal function in rats with bilateral ureteral obstruction

To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Die proximale Femurfraktur des älteren Patienten

In a retrospective study, 1.173 fractures of the proximal femur, which had been treated surgically, were analysed in two periods from 1975 to 1991 and from 1992 to 2000. The influence on mortality of preoperative risk factors and primary treatment with total hip replacement (THR), even in cases of pertrochanteric fractures, was analysed by stepwise logistic regression. In the later period, mortality within 90 days was 13.1%, and within 1 year 22.2%. Rejection of hemiendoprosthesis in high-risk patients with intracapsular fractures increased the mortality rate from 6.3% to 11.8%. The introduction of dynamic hip screws instead of Ender nails led to a reduction of mortality from 16.5 to 7.1%. Higher mortality after THR (27.6%) compared to osteosynthesis (15.5%) in pertrochanteric femur and lateral neck fractures was due to higher age and increased risk factors. Although the influence of some risk factors could be reduced, age, sex and morbidity influenced the outcome more than surgical treatment. THP, even after pertrochanteric fractures, is reasonable if it guarantees a quick and enduring mobilisation of the patient. Bicentric bipolar prostheses are recommended for high risk patients.