Vitamin K and the urogenital tract

Solubilized microsomes from bovine liver, kidney and testis were compared with regard to their content of vitamin-K-dependent carboxylase, the presence of endogenous vitamin K as well as that of endogenous carboxylatable precursor proteins. The isolation and purification of these protein substrates was not successful. Using antibodies against various well characterized proteins containing gammacarboxyglutamic acid (Gla), we were able to identify precursors of the blood coagulation factors II, IX and X in liver microsomes. The nonhepatic proteins could not be identified in this way. Gla-containing proteins, however, were isolated from human sperm, urine and renal stones. It was demonstrated that - like osteocalcin - also the urinary Gla protein inhibits the precipitation of various calcium salts from supersaturated solutions. The concentration of the urinary Gla protein (16 mg/l) in human urine is well above the concentration required for the in vitro inhibition of salt precipitation.     

Visceral diabetic neuropathy of the urogenital tract

The article deals with issues of diabetic autonomous neuropathy (DAN) in the urogenital tract (UGT), and brings attention to the ethiopathogenesis of diabetic polyneuropathy. It provides a synopsis of autonomous neuropathy and deals, in more detail, with its manifestations in the UGT. The different symptoms of the disorder are addressed, the need for timely diagnosis is pointed out as the prerequisite for a successful therapy, and the necessity for interdisciplinary cooperation in dealing with this health issue is exposed.     

Ankylosing spondylitis and infections of the female urogenital tract

Thirty-two female patients with confirmed ankylosing spondylitis (AS) and 33 women of similar age with pure ileitis terminalis Crohn were examined for genitourinary infection. Urethral syndrome was found in 15 out of 32 patients with AS: 11 of them had urethritis and 4 urethritis associated with vaginitis. Five women of the control group suffered from urethritis. In all cases with genitourinary infection, Chlamydia trachomatis was isolated. By comparing the AS-patients (urogenital infection group and the non-infected group) with regard to other present clinical parameters, it was found, as expected, that the erythrocyte sedimentation rate in the 1st hour was significantly higher in the infected group. In addition, the infected patients had a significantly higher incidence of enthesopathy, involvement of the spinal column, and higher C-reactive protein values (CRP ≥ 5 mg/l). A family history of AS was equally present. Other clinical parameters, such as inflammatory involvement of the joints and HLA-B27 correlation, did not differ significantly between infected and non-infected patients. Received: 22 July 1997 / Accepted 9 January 1998     

Effects of naproxen on connective tissue changes in the adjuvant arthritic rat

The Freund's adjuvant-injected rat shares a number of features with the arthritis patient, viz the presence of a proliferative synovitis, joint swelling, and cartilage and bone erosion. Naproxen, a prostaglandin synthetase inhibitor which is an effective antiinflammatory agent in laboratory animals and humans, was evaluated as an inhibitor of connective tissue destruction in this model by use of radiologic and histopathologic analyses. Sixteen days after rats were injected with Freund's complete adjuvant, marked joint swelling was noted. On day 17, vehicle or naproxen, 7 mg/kg/day, was administered orally. Twenty-eight days later vehicle-treated animals demonstrated the following pathologic changes in their hindpaws; swelling, cartilage loss, large amounts of pannus within the joint spaces, osteoporosis, bone erosions, periosteal new bone formation, heterotopic ossification, and bony ankylosis. Rats treated 28 days with naproxen had significantly milder disease than the vehicle controls. The incidence of severe juxtaarticular bone destruction was 10/10 in the vehicle controls versus 2/10 of the drug-treated group (P less than 0.01). A comparable reduction in cartilage erosion, incidence of pannus, and new bone formation was noted in the drug-treated group. These effects may relate to an inhibition of prostaglandin biosynthesis; prostaglandins have been shown to: 1) stimulate collagenase secretion from macrophages, 2) stimulate bone resorption in vivo and in vitro, and 3) diminish proteoglycan synthesis in cartilage.     

The course of adjuvant disease in rats of the strain AF/Han-EMD-SPF]

The development of articular and osseous lesions in AF/Han-EMD-SPF breed rats with adjuvant disease was studied by morphological methods. At the noninjected side arthritic lesions with eventual progressive joint destruction appeared about the tenth day after adjuvant injection. Nearly simultaneously an incipient tumorous osteomyelitis in the bones both of injected and non-injected side was observed. Since epitheloid granuloma were also seen in the periarticular tissue of some animals the authors believe that all lesions in adjuvant arthritis are caused by a widespread dissemination of the injected complete adjuvant.     

Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities

Ulcerative colitis (UC) and Crohn's disease (CD), the primary constituents of inflammatory bowel disease (IBD), are precipitated by a complex interaction of environmental, genetic, and immunoregulatory factors. Higher rates of IBD are seen in northern, industrialized countries, with greater prevalence among Caucasians and Ashkenazic Jews. Racial gaps are closing, indicating that environmental factors may play a role. IBD is multigenic, with the most clearly established genetic link between certain NOD2 variants and CD. Regardless of the underlying genetic predisposition, a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the pathogenesis of IBD, especially CD. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or virus or a defective mucosal barrier. The characteristic inflammatory response begins with an infiltration of neutrophils and macrophages, which then release chemokines and cytokines. These in turn exacerbate the dysfunctional immune response and activate either TH1 or TH2 cells in the gut mucosa, respectively associated with CD and, less conclusively, with UC. Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD.     

Age dependent changes in the sperm population and fertility in the male rat

The entire reproductive tract was devoid of spermatozoa during the first 42 days of life. The first appearance of spermatozoa was detected in the caput epididymidis of 45-day old rats and in the cauda epididymidis of 52-day or older rats. The number of spermatozoa in the reproductive tract increased with age. The sperm population reached its maximum in the caput epididymidis by day-72 and in the caud epididymidis by day-100. These high levels were maintained beyond 450 days of age. Fifty-two day old male rats failed to impregnate the female. Although male rats of 62-500 days were able to sire litters, the peak reproductive period was found to be between days 100-270, during which the number of young per litter ranged between 11-16. Towards advanced age the litter size dropped to 8. The lower fertility in the males of advanced age might be due to a lower proportion of fertile spermatozoa, a change in the physiology of epididymis or an altered sperm transport in the reproductive tract.     

Age dependent changes in the sperm population and fertility in the male rat

The entire reproductive tract was devoid of spermatozoa during the first 42 days of life. The first appearance of spermatozoa was detected in the caput epidiymidis of 45-day old rats and in the cauda epididymidis of 52-day or older rats. The number of spermatozoa in the reproductive tract increased with age. The sperm population reached its maximum in the caput epididymidis by day-72 and in the cauda epididymidis by day-100. These high levels were maintained beyond 450 days of age. Fifty-two day old male rats failed to impregnate the female. Although male rats of 62–500 days were able to sire litters, the peak reproductive period was found to be between days 100–270, during which the number of young per litter ranged between 11–16. Towards advanced age the litter size dropped to 8. The lower fertility in the males of advanced age might be due to a lower proportion of fertile spermatozoa, a change in the physiology of epididymis or an altered sperm transport in the reproductive tract.     

Pulmonary veno-occlusive disease: a case report and a review of therapeutic possibilities.

We describe the observation of a 12 yr old girl who died of pulmonary veno-occlusive disease (PVOD). Diagnosis was based on histological examination of an open lung biopsy. The differential diagnosis, pathogenesis and possible therapies are discussed. Although medical therapy can sometimes give some temporary relief, lung transplantation might offer these patients a better chance of survival and a better quality of life.