Israel Medical Association Journal

Background: Decreased heparan sulfate proteoglycan content of the glomerular basement membrane has been described in proteinuric patients with diabetic nephropathy. Heparanase is an endo-b-D-glucuronidase that cleaves negatively charged heparan sulfate side chains in the basement membrane and extracellular matrix.

Objectives: To investigate whether urine from type I diabetic patients differs in heparanase activity from control subjects and whether resident glomerular cells could be the source of urinary heparanase.

Methods: Using soluble ³⁵S-HSPG[1] and sulfate-labeled extracellular matrix we assessed heparanase activity in human glomerular epithelial cells, rat mesangial cells, and urine from 73 type I diabetic patients. Heparanase activity resulted in the conversion of a high molecular weight sulfate-labeled HSPG into heparan sulfate degradation fragments as determined by gel filtration analysis.

Results: High heparanase activity was found in lysates of both epithelial and mesangial cells. Immunohistochemical staining localized the heparanase protein to both glomeruli capillaries and tubular epithelium. Heparanase activity was detected in the urine of 16% and 25% of the normoalbuminuric and microalbuminuric diabetic patients, respectively. Urine from 40 healthy individuals did not posses detectable heparanase. Urinary heparanase activity was associated with worse glycemic control.

Conclusion: We suggest that heparanase enzyme participates in the turnover of glomerular HSPG. Hyperglycemia enhances heparanase activity and/or secretion in some diabetic patients, resulting in the loss of albumin permselective properties of the GBM[2].

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[1] HSPG = heparan sulfate proteoglycan

[2] GBM = glomerular basement membrane

Systemic infection or inflammation causes a decrease in intestinal iron absorption and impairs the release of recycled iron from macrophages. Decreased availability of iron may deny this essential element to invading pathogens and may inhibit their multiplication and other metabolic processes but also results in anemia of chronic disease. This article reviews recent discoveries that shed light on the regulation of iron metabolism during infection and iron overload, and point to the central role of a newly discovered peptide, hepcidin. Evidence to date indicates that hepcidin is a negative regulator of intestinal iron absorption, placental iron transport, and the release of iron from macrophages that recycle iron from senescent red cells. It may also be the central mediator of iron sequestration during infections and inflammatory states and the mediator of anemia of chronic disease. Rapid progress in this area is a good example of the beneficial effects of improvements in peptide analysis and chemistry, advances in genomics, and the increasing use of transgenic mice to determine the function of newly discovered genes and proteins.

The formerly prevalent concept that intact autoantibodies could not penetrate into viable cells has been defeated by a large amount of experimental findings and clinical observations that indicate otherwise. The penetration of autoantibodies into living cells seems to participate in the pathogenesis of diverse autoimmune diseases, but it may also play a physiological role in healthy individuals. Although the fine mechanisms of the phenomenom remain to be elucidated, the potential use of penetrating autoantibodies as vectors to deliver molecules into cells, with diverse therapeutic purposes, has gained growing interest during the last few years.

Background: Urinary tract infection is one of the most common bacterial infections. Since antibiotics are given empirically, it is necessary to assess the distribution and susceptibility of the microorganisms in each case.

Objectives: To evaluate the demographic characteristics of ambulatory patients with UTI, the distribution and susceptibility of uropathogens, and the risk factors associated with trimethoprim-sulfamethoxazole resistant bacteria in women.

Methods: During 12 days in August 1997 all the urine cultures sent to the Tel-Hanan Laboratory (Haifa) were evaluated. Demographic characteristics of the patients, their underlying diseases and the previous use of antibiotics were obtained.

Results: During the 12 day survey 6,495 cultures were sent for evaluation. Of the 1,075 (17%) that were positive 950 were included in the study; 83.7% were from females, of whom 57% were ≥50 years old. Escherichia coli was the most common pathogen, with 74.7% in the female and 55% in the male population; 86.2% of the E. coli were resistant to amoxicillin, 38.8% to cephalexin and 46.8% to TMP-SMX. Cefuroxime (4.2%), ofloxacin (4.8%), ciprofloxacin (4.8%) and nitrofurantoin (0.4%) showed the lowest rates of resistance. By a multivariant analysis, post-menopause and recurrent UTI were found to be independent factors related to TMP-SMX resistance in women.

Conclusion: In northern Israel, ampicillin, cephalexin and TMP-SMX cannot be used empirically in the treatment of community-acquired UTI. Post-menopause and recurrent UTI are independent factors associated with TMP-SMX resistant pathogens in women.

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UTI= urinary tract infection

TMP-SMX= trimethoprim-sulfamethoxazole