A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

Over 18% of pregnant women are affected by diabetes mellitus (DM) and Insulin has been the commonest drug used in its treatment. There are reports of noncompliance to insulin due to trypanophobia, with suggestions for the use of oral hypoglycaemic agents (OHAs). However, the opposing views about the benefits and risk of oral hypoglycaemic agents (OHAs) warrant a continuous search for an alternative regimen. Therefore, this study is aimed at comparing the antidiabetic effects of d-ribose-l-cysteine (riboceine) with vildagliptin, glibenclamide, metformin, glipizide and insulin in diabetes in pregnancy. Forty (40) female Sprague-Dawley (SD) rats were mated with twenty (20) male SD rats. Diabetes was induced by streptozotocin and the female SD rats were divided into 8 groups of five (5) rats each. The animals were administered either of the OHAs vildagliptin, glibenclamide, metformin, glipizide and riboceine for a period of 19 gestational days. The results showed that streptozotocin (STZ) significantly (p < 0.05) decreased the weights of the animals, increased malondialdehyde, blood glucose levels and altered reproductive hormones. These effects of STZ were better ameliorated in animals that received insulin and riboceine compared to the other OHAs. While progesterone levels were significantly (p < 0.05) higher in animals that received riboceine compared to insulin. Glibenclamide increased (p < 0.05) foetal weights compared to non-diabetic animals. In conclusion, glibenclamide may be a threat to mother`s life in the management of diabetes in pregnancy however, riboceine as well as vildagliptin, metformin and glipizide are effective oral hypoglycaemic agents which could serve as a potent adjuvant comparable to insulin in the management of diabetes during gestation.

Secondary solid cancer screening following hematopoietic cell transplantation.

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

Contrasting effects of A1 and A2b adenosine receptors on adipogenesis.

BACKGROUND: Adenosine mediates its actions through four G protein-coupled receptors, A1, A2a, A2b and A3. The A1 receptor (A1R) is dominant in adipocytes where it mediates many actions that include inhibition of lipolysis, stimulation of leptin secretion and protection against obesity-related insulin resistance. OBJECTIVE: The objective of this study is to investigate whether induced expression of A1Rs stimulates adipogenesis, or whether A1R expression is a consequence of cells having an adipocyte phenotype. METHODOLOGY: Human A1R and A2b receptors (A2bRs) were stably transfected into a murine osteoblast precursor cell line, 7F2. Adipogenesis was determined by lipid accumulation and expression of adipocyte and osteoblast marker molecules. Adenosine receptor expression and activation of associated signal molecules were also evaluated as 7F2 cells were induced to differentiate to adipocytes. RESULTS: 7F2 cells transfected with the A1R showed increased adipocyte marker mRNA expression; lipoprotein lipase and glycerol-3-phosphate dehydrogenase were both upregulated, whereas the osteoblast marker alkaline phosphatase (ALP) was downregulated. When cultured in adipocyte differentiating media, such cells also showed increased adipogenesis as judged by lipid accumulation. Conversely, A2bR transfection stimulated osteocalcin and ALP expression, and in addition, adipogenesis was inhibited in the presence of adipocyte differentiation media. Adipogenic differentiation of naive 7F2 cells also resulted in increased expression of the A1R and reduced or modified expression of the A2a and A2bR. The loss of A2 receptors after adipogenic differentiation was accompanied by a loss of cyclic adenosine monophosphate and ERK1/2 signalling. CONCLUSION: These data show that expression of A1Rs induced adipocyte differentiation, whereas A2bR expression inhibited adipogenesis and stimulated an osteoblastic phenotype. These data suggest that targeting A1 and A2bR could be considered in the management of obesity and diabetes. Targeting adenosine signal pathways may be useful in treatment strategies for diseases in which there is an imbalance between osteoblasts and adipocytes.

The development and regression of deciduosarcomas and other lesions caused by estrogens and progestins in rabbits.

A series of experiments were conducted to study the histopathological effects of a combination of exogenous estrogens and progestins in mature rabbits. Estradiol (14-45 microg/day) and levonorgestrel (30-233 microg/day) were administered by intravaginal or subdermal Silastic devices for various time intervals to study the development of lesions with time and to determine if lesions regressed following withdrawal of the steroids. The origin of splenic decidual tumors (primary or metastasis from the uterus) was determined by administering the same steroid combination to castrated male rabbits. It was determined that uterine decidualization is present after 7 days of steroid treatment and that neoplasms of decidual cells may appear in the uterus after only 30 days of steroid administration. Decidual changes were observed frequently in uterine arteries, often concurrent with infarct-like areas of necrosis of the uterine wall. Withdrawal of contraceptive steroids for 14-120 days after 60 days' administration resulted in atrophy and disappearance of decidual cells and decidual tumors. Decidual neoplasms developed in the spleen of all castrated male rabbits given subdermal steroids, demonstrating that these tumors can arise as primary neoplasms of the spleen. The foregoing lesions appear to be peculiar to the rabbit and, together with previous data, suggest the rabbit to be a poor model for evaluating the effects of contraceptive steroids in other species.

Apoptosis in human immunodeficiency virus-associated nephropathy.

Focal segmental glomerulosclerosis associated with human immunodeficiency virus nephropathy (HIVFGS) involves glomeruli, tubules, and interstitium. Its pathogenesis is unknown, but HIV peptides may be critical in its development. Human immunodeficiency virus peptides and peptide-antibody complexes are immunomodulatory, and are associated with apoptosis in lymphoid cells. To determine whether apoptosis is present in HIVFGS, renal biopsy specimens of eight patients with HIVFGS were compared with those of 10 patients with idiopathic focal glomerulosclerosis (FGS) using the Apoptag kit (Oncor, Gaithersburg, MD), which detects single cell apoptosis in formalin-fixed tissue by staining 3' nucleosome fragments with digoxigenin-labeled nucleotides after terminal deoxynucleotidyl transferase enzyme treatment. Apoptosis was scored per glomerulus, in total renal tissue sectioned, and in tubules and interstitium per square millimeter using a computerized digital image analyzer. There was no difference between the number of apoptotic cells per glomerulus or per square millimeter of interstitium in patients with FGS and HIVFGS. There were greater numbers of tubular apoptotic cells per square millimeter (2.1 +/- 0.9 v 0.15 +/- 0.08; P = 0.03) in HIVFGS compared with idiopathic FGS. The difference between apoptotic cells per total square millimeter of renal tissue (2.8 +/- 1.2 v 0.7 +/- 0.3) approached significance (P = 0.066). Apoptosis may be associated with the pathogenesis of HIV nephropathy and may be an important determinant of the tubular disease in HIVFGS.

Macrophages in human immunodeficiency virus-associated kidney diseases.

Human immunodeficiency virus (HIV)-associated nephropathies are characterized by renal immune cell interstitial infiltration in patients with peripheral T-cell depletion. Since interstitial inflammation may mediate cytokine-induced fibrosis, we evaluated the immune cell population in the interstitium and glomeruli in renal biopsy tissue from 10 HIV-infected patients with focal segmental glomerulosclerosis (HIVFGS), staining renal biopsy specimens for UCHL-1 (a T-cell marker), OPD4 (predominantly a T helper-cell marker), PG-M1 (a macrophage marker), and L26 (a B-cell marker), and comparing them with renal tissue specimens from patients with HIV-associated immune complex glomerulonephritis (ICD) and from uninfected patients with FGS. Five fields comprising 0.2 mm2 were examined at a magnification of x400, a total area of 1 mm2. Total immune cells were estimated as the sum of UCHL-1, L-26, and PG-M1 cells. The T helper to suppressor (H/S) ratio was estimated as OPD4/(UCHL-1 - OPD4) lymphocytes. Tubular interstitial infiltrate was variable but dense in the majority of the infected biopsies, and was mild to moderate in all uninfected cases. The proportion of interstitial macrophages was greater in biopsy specimens from patients with HIVFGS than in those with HIVICD. In contrast, there was a greater percentage of B cells in the infiltrate in HIVICD compared with HIVFGS. Although there were fewer immune cells in whole glomeruli compared with 1 mm2 interstitium, macrophages were the predominant cells in glomeruli. B lymphocytes were generally absent in glomeruli in infected tissue, a pattern similar to uninfected tissue. The blood H/S ratio in HIV-infected patients was 0.2 +/- 0.03.(ABSTRACT TRUNCATED AT 250 WORDS)

Membranoproliferative glomerulonephritis in a patient treated with interferon-alpha for human immunodeficiency virus infection.

Several renal pathologic entities have been reported to be associated with human immunodeficiency virus (HIV) infection. The most common is focal glomerulosclerosis, but several different types of glomerulonephritis have been observed in patients with HIV infection and the acquired immunodeficiency syndrome. The mechanisms involved in the pathogenesis of the kidney disease remain obscure. We studied an HIV-infected patient treated with interferon-alpha who had developed proteinuria and membranoproliferative glomerulonephritis to determine whether the renal disease was associated with HIV infection or with chemotherapy. Circulating HIV antibodies were assessed by enzyme-linked immunosorbent assay; circulating immune complexes (CICs) were measured by C'1q assay and isolated by polyethylene glycol precipitation, then subjected to gel electrophoresis and immunochemical analysis. Renal biopsy tissue underwent acid elution, and the eluates were analyzed similarly. In addition the eluted antibody and the antibody from the CIC were assessed by immunodiffusion with eluate and immune complex antigens. A single CIC was detected, which was composed of an immunoglobulin G antibody complexed to a 26-kd protein antigen that was shown to be interferon-alpha. Eluate from the renal biopsy tissue demonstrated identical material, which cross-reacted with the components of the isolated CIC. Immune complex renal diseases, such as membranoproliferative glomerulonephritis, may be related to biologic response modifying agents in patients with HIV infection. The relative roles of their biologic response modification and the disordered immunoregulation seen in such patients in the pathogenesis of the renal disease is unclear. Renal biopsy is necessary to assess the etiology of the renal disease in HIV-infected patients.

A comparison of the usefulness of electron microscopy and immunohistochemistry. One laboratory's experience.

As a quality assurance measure, the usefulness of transmission electron microscopy (EM) and immunohistochemistry (IHC) in our surgical pathology laboratory was compared. The surgical pathology reports from 150 consecutive neoplasms that were examined by both EM and IHC were reviewed. Based on the reported clinical histories, final diagnoses, light microscopy results, and the findings by EM or IHC, the contributions of EM and IHC were classified as "helpful" or "not helpful" for each specimen. Electron microscopy was helpful (92%) more often than was IHC (73%). Electron microscopy was most useful in further classifying poorly differentiated carcinomas, while IHC was particularly useful in classifying poorly differentiated neoplasms. Electron microscopy and IHC were of limited value in identifying the origin of metastatic carcinomas of an uncertain primary. All cases determined to be "not helpful" by either modality were further analyzed to establish a reason for the lack of information provided in each case. This analysis demonstrated a need for improved technical quality and ordering patterns of immunohistochemical stains in our laboratory.

S-100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immunohistochemical study.

S-100 protein is considered a characteristic immunohistochemical marker for all nevomelanocytic lesions, in which it is expected to be present consistently. We reviewed 17 cases of malignant melanomas that previously tested negative for S-100 protein. They were reevaluated by light microscopy, a broad panel of immunohistochemical reagents including monoclonal and polyclonal antibodies to S-100 protein, and electron microscopy. On reexamination, five of the 17 cases were reclassified as non-melanoma tumors, and eight of the 17 cases were found to be positive for S-100 protein (six with monoclonal and eight with polyclonal antibodies) and HMB-45 antigen, consistent with melanoma. The remaining four cases repeatedly tested negative for S-100 protein despite various antigen enhancement methods, but they were positive for HMB-45 antigen and contained premelanosomes or melanosome-like structures by electron microscopy. Two of these repeatedly S-100 negative melanomas were acrally located; although the numbers are small, a possible relationship to a specific anatomic location cannot be excluded. These findings suggest that in a small subset of melanomas S-100 protein is either not fully expressed or is below the level that can be detected by routine immunohistochemistry. We also conclude that in the majority of the initially S-100-negative cases of melanomas, the misdiagnosis may occur due to the use of an incomplete immunohistochemical panel, technical reasons, or the inherent variability of tissue expression of S-100 protein.

HIV-associated immune-mediated renal disease.

Although focal glomerulosclerosis is the most common renal disease, other proliferative glomerulonephritides are encountered in HIV-infected patients. We studied four HIV-infected patients with renal insufficiency, proteinuria, and proliferative glomerulonephritis, consistent with immune-mediated disease, to investigate the role of the virus and immune complexes in the pathogenesis of the nephropathy. Circulating immune complexes (CICs) and HIV-reactive antibodies were measured and characterized in each patient. Renal biopsy tissue was acid eluted, and the eluate analyzed. DNA extracted from biopsies was subjected to the polymerase chain reaction (PCR) to detect HIV genome. CICs were detected in each patient: an IgA-p24 HIV antigen complex and an IgG antibody-gp 120 HIV antigen complex in two patients; two patients had an IgG-p24 HIV antigen complex. Identical complexes were eluted from renal tissue in the first three patients; p24 HIV antigen, and complement from the fourth. The eluted antibodies reacted with the HIV antigens from the isolated CICs. Direct immunofluorescence for viral antigen in the eluted glomerular tissue revealed HIV antigens; PCR confirmed the presence of gag genome in all four biopsies. We conclude both circulating and in-situ HIV antigen-specific immune complexes may be associated with glomerulonephritis in HIV infected patients. Viral incorporation into renal tissue may be important in the pathogenesis of HIV-associated renal disease.

Viral DNA in microdissected renal biopsy tissue from HIV infected patients with nephrotic syndrome.

Focal glomerulosclerosis (FGS) has been considered as HIV-associated nephropathy, a specific renal complication of infection. To determine whether renal disease in HIV infected patients has one highly prevalent pathologic expression, and whether renal parenchymal viral genomic incorporation affects pathologic outcome, we reviewed renal biopsies performed at our center. Twenty-eight HIV infected patients with nephrotic range proteinuria underwent renal biopsy for diagnosis of renal disease: 85.7% led homosexual or bisexual lifestyles; 10.7% admitted to intravenous drug use; and 85.7% were Black. Only 53.6% had FGS; 28.6% had glomerulonephritis. Two patients had diabetic renal disease; 93.3% of patients with FGS and 87.5% of patients with glomerulonephritis were Black. Paraffin slides of twenty-two of the patients' renal biopsies were evaluated by polymerase chain reaction (PCR) for the presence of HIV DNA, using primers and probes to the gag gene, detected by liquid hybridization and polyacrylamide gel electrophoresis. Twenty-one of the twenty-two evaluated tissue specimens showed the presence of HIV DNA. Microdissection studies of glomeruli, tubules, interstitial cells and infiltrating inflammatory cells showed the presence of HIV genome in all but interstitial cells. HIV infected patients without renal disease also had positive PCR evaluations of microdissected tissue, while non-infected patients were all negative. We conclude that although focal glomerulosclerosis is the most common renal pathologic lesion in patients with HIV infection and nephrotic range proteinuria, glomerulonephritis is a relatively frequent finding. HIV genome is present in renal tissue in HIV infected subjects with nephrotic range proteinuria, but is also found in HIV infected subjects without nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Degenerative ("ancient") changes in benign cutaneous schwannoma. A light microscopic, histochemical and immunohistochemical study.

We studied the degenerative "ancient" changes in 19 cases of benign cutaneous schwannoma (BCS). Using conventional and immunohistochemical stains, we found (a) degenerative changes in 15 of 19 BCS; (b) prominent vascular abnormalities in 11 of 15 BCS; and (c) cytologic atypia in 15 of 19 BCS, without mitotic figures. We concluded that (1) degenerative, i.e., "ancient" changes are common in BCS and are qualitatively similar to those described in cellular schwannoma; (2) vascular abnormalities may be related to these degenerative changes; (3) cytologic atypia is commonly associated with "ancient" changes in BCS, but BCS is less cellular and has few if any mitotic figures as opposed to cellular schwannomas; and (4) the changes in "ancient" schwannoma do not indicate a "cellular" schwannoma.

Nephrotic syndrome associated with chronic persistent hepatitis B in an HIV antibody positive patient.

Several renal diseases have been reported to complicate both hepatitis B and human immunodeficiency virus infection. Establishing the exact renal diagnosis in patients with multiple viral infections requires renal biopsy. Exposure to human immunodeficiency virus may not determine renal histopathology. Although exact prognosis depends on a definitive diagnosis, treatment options may be limited in the face of several viral infections and concurrent exposure to human immunodeficiency virus.

El aceite esencial de atamisqui (Atamisquea emarginata, M.) y su poder antiseptico. / The essential oil of atamisqui (Atamisquea emarginata,M.) and its antiseptic property

En la presente comunicacion se obtiene el aceite essencial de atamasqui(Atamasquea emarginata,M.) y se detallan sus caracteres organolepticos y algumas constantes fisicas y ensayos quimicos cualitativos. Se determina su poder antiseptico para Staphylococcus aureus, Salmonella typhi y Candida albicans, y sus respectivos coeficientes de fenol segun la tecnica de Ruehle y Brewer (l931).Se concluye que el aceite esencial de atamisqui tiene propiedades antipecticas: que existe una neta diferencia de accion segun el germen sobre el que actue; y teniendo en cuenta los microorganismos ensayados solamente, se podria inferir que el mismo es mucho mas activo para bacterias que para hongos, y entre las primeras, para un germen gramnegativo que para uno grampositivo

Pancreatic necrosis in progressive systemic sclerosis.

Fatal pancreatic necrosis, secondary to extensive acute arteritic changes, is reported in a case of progressive systemic sclerosis. The patient presented first with hypertension and renal involvement, with active vascular lesions demonstrated by biopsy. The renal lesion at necropsy was inactive, showing the characteristic concentric fibrosis only, while the pancreatic vascular lesions were both chronic proliferative and acute in type.

Bullous dermatosis and systemic lupus erythematosus in a 15-year-old boy.

A 15-year-old boy had a bullous eruption suggestive of bullous pemphigoid and established systemic lupus erythematosus (SLE). Direct immunofluorescence studies of the bullae and adjacent skin revealed the linear deposition of IgG and complement localized to the basement membrane zone. Indirect immunofluorescence examination of the serum failed to reveal circulating basement membrane zone antibodies. The differential diagnosis of the bullous eruption is reviewed, and the problem of diagnosis in cases of coexistent bullous disease and SLE is discussed.

Enterovirus infection in a semi-closed community.

Infection with enteroviruses was studied over a 61-week period (during 1960-61) in a semi-closed child community in the Detention Home of the Allegheny County Juvenile Court in Pittsburgh, Pennsylvania. While most of the viruses isolated were known adeno- and enterovirus types, three apparently represent new enterovirus types or 'prime strains'. Viruses were isolated in all but 6 weeks of the 61-week study period from the gastro-intestinal tracts of 110 children out of a total population of 514 (21%); of these 110, 24 children (22%) excreted virus at the time of admission. The population averaged 37 children (more than half of whom were under 5 years of age), with a turnover of about nine per week. Spread of infection in this community on introduction of a new virus was demonstrated, with virus shedding of variable duration after infection. Thirteen of the 110 positive children (12%) showed mixed virus infections. During the entire study period, no clinical diarrheal illness was found associated with the viral infections detected.

Ileojejunitis in a pair of identical twins.

A pair of identical twin brothers with identical white and red blood cell antigens and diffuse ileojejunitis is reported. One brother initially presented with granulomatous gastritis, presumably Crohn's disease of the stomach. The relationship of diffuse ileojejunitis to Crohn's disease and the suspected genetic predisposition to develop Crohn's disease are briefly discussed.