Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

OBJECTIVE: Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. MATERIALS AND METHODS: Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. RESULTS: Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. CONCLUSIONS: This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

[Difficulty in diagnosis of a cardiogenic shock with thrombotic and sub-occluded LAD. A train can hide another one!] / Difficulté diagnostic d'un choc cardiogénique sur une sub-occlusion thrombotique de l'IVA. Un train peut en cacher un autre !

The pheochromocytome is a localized tumor at the level of the medullosurrenale in 85% of the cases. The clinical presentation is very variable. Severe Heart failure presentation can be the mode of revelation in 2% of the cases. We present the case of a patient admitted for refractory cardiogenic shock correlated to pheochromocytome tumor. The difficulty of this rare clinical presentation was to confirm rapidly and in emergency this diagnosis in the same time when the patient presents a persistante and severe cardiogenic chock after finding a sub-occluded and thrombotic LAD coronary artery and which was treated by thrombectomy and coronary revascularization. The surgical treatment of this tumor is considered to be a quickly saving treatment. It allows a fast recovery of the cardiac function.

Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors.

Adrenomedullin mediates early phase angiogenesis induced diabetic nephropathy in STZ diabetic rats.

OBJECTIVE: The implication of pro-angiogenic factors including vascular endothelial growth factor (VEGF) and its receptor flk-1 has been reported in diabetic nephropathy as early event. Adrenomedullin (AM), a potent vasodilator peptide, enhances angiogenesis and high levels were seen in diabetic animals and humans. However, its exact role in diabetic nephropathy is unclear. The present study investigated the effects of adrenomedullin receptor antagonist (ADM-52-22) on the early phase angiogenesis-induced diabetic nephropathy. MATERIALS AND METHODS: 28 male Wistar rats were divided into: 1) Control non-diabetic, 2) Streptozotocin (STZ)-induced diabetic rats (55 mg/kg, i.p.), 3) Control non-diabetic+ADM-52-22, and 4) STZ-diabetes+ADM-52-22 (7 per group). ADM-52-22 was infused for two weeks (250 µg/rat/day, i.p.). RESULTS: Diabetes caused an increase in kidney weight, renal VEGF levels, 24 hr urinary protein and nitric oxide excretion and hyperfiltration indicated by creatinine clearance (CrCl). ADM-22-52 reduced the rise in CrCl, total urinary protein and renal hypertrophy in diabetic rats, and attenuated early angiogenic response to diabetes: CD31 staining, flk1 protein and VEGF renal levels. CONCLUSIONS: These results show that AM through its receptor mediates early angiogenesis-induced diabetic nephropathy which attributes to the early changes as hyperfiltration and hypertrophy.

The effects of a loin muscling quantitative trait locus (LoinMAX™) on carcass and VIA-based traits in crossbred lambs.

LoinMAX (LM) is a quantitative trait locus (QTL), which was found to be segregated in Australian Poll Dorset sheep, and maps to the distal end of sheep chromosome 18. LM-QTL was reported to increase Musculus longissimus dorsi area and weight by 11% and 8%, respectively. The aim of this study was to comprehensively evaluate the direct effects of LM-QTL in a genetic background typical of the stratified structure of the UK sheep industry, before it can be recommended for use in the United Kingdom. Crossbred lambs, either non-carriers or carrying a single copy of LM-QTL, were produced out of Scottish Mule ewes (Bluefaced Leicester × Scottish Blackface) artificially inseminated with semen from two Poll Dorset rams that were heterozygous for LM-QTL. Unexpectedly, one of these rams was also heterozygous for a QTL that affects the overall carcass muscling (MyoMAX™). This was accounted for by nesting MyoMAX™ status (carrier or non-carrier) within sire in the statistical analysis. Lambs were weighed and scanned by using X-ray computed tomography (CT) at an average age of 113 days. Ultrasound scan measurements, along with lamb weights, were taken at an average age of 140 days and lambs were then slaughtered. Carcasses were weighed and classified for fat cover and conformation scores, based on the Meat and Livestock Commission (MLC) carcass classification scheme, and then scanned by using a video image analysis (VIA) system. M. longissimus lumborum (MLL) width, as measured by CT scanning, was greater (P < 0.05) in lambs heterozygous for LM-QTL compared with non-carriers. MLL in LM-QTL carrier lambs was also significantly deeper, as measured by both ultrasound muscle depth at the third lumbar vertebrae (+3.7%; P < 0.05) and CT scanning at the fifth lumbar vertebrae (+3.4%; P < 0.01). Consequently, MLL area, was measured by using CT scanning, was significantly higher (+4.5%; P < 0.01) in lambs carrying a single copy of LM-QTL compared with non-carriers. Additional traits measured by CT, such as leg muscle dimensions, average muscle density and tissue proportions, were not significantly affected by LM-QTL. LM-QTL did not significantly affect total carcass lean or fat weights or MLC conformation and fat score classifications. Using previously derived algorithms, VIA could detect a significant effect of the LM-QTL on the predicted weight of saleable meat yield in the loin primal cut (+2.2%; P < 0.05), but not in the other primal cuts, or the total carcass.

Functional Mx protein does not prevent experimental biliary atresia in Balb/c mice.

Biliary atresia (BA) is a rare cholestatic disease, which manifests itself in the form of inflammation of the liver and bile ducts in newborns, with an unknown etiology and a poor outcome. Mx proteins, which are mediators of innate, antiviral resistance induced by type I interferon, were recently detected in the livers of children with BA. Therefore, the aim of this study was to examine whether the expression of Mx protein could affect the course of experimental BA in mice. A total of 185 newborn Balb/c mice (expressing dysfunctional Mx protein) and Balb/c-Mx+-A2G mice (with functional Mx protein) were intraperitoneally infected with rhesus rotavirus (RRV) or injected with saline solution as controls. They were sacrificed if they showed signs of cholestasis or at three weeks after infection. The expression of hepatic Mx protein was detected by immunostaining (POX) and the hepatic virus load was determined. There was no significant difference in the incidence of cholestasis between wild-type Balb/c mice and Balb/c-Mx+-A2G mice (67 % vs. 65 %). However, Mx protein was highly expressed in Balb/c-Mx+-A2G mice with BA phenotype, but not in wild type Balb/c mice or disease-free Balb/c-Mx+-A2G mice despite RRV infection. The difference in the hepatic virus load was not statistically significant in mice with BA. In conclusion, Mx protein does not prevent newborn Balb/c mice from developing biliary atresia after RRV infection. However, the expression of Mx protein is independent of the hepatic virus load and could be used as a marker of BA in humans, as well as in the RRV model.

[Surgical management of varicose ulcers]. / Chirurgická léba zilních bércových viedu.

One of the most often diseases of the European population is the venous chronic leg ulcer. It requires a long-term and expensive therapy. Basic elements of the therapy are elastic banding of the leg, diuretics, antibiotics and local treatment. In some cases a profit can be acquired from surgical procedure, which includes the stripping and/or crossectomy of the saphenous vein or the subfascial ligation of insufficient perforators and skin grafting (two phases operation). This procedure shorts the time of therapy and prevents the ulcer recurrence, because it resolves the reason and the results of the disease. We present 22 patients treated by this cure during the last 3 years at our surgery department of the 3rd faculty of medicine Charles University in Prague. 21 patients (95.5%) are healed.

[Postoperative fasciitis after laparotomy]. / Pooperacní fasciitis po laparotomii.

Postoperative infectious and necrotizing abdominal wall fasciitis is a serious wound complication. Authors present own analysis of their experience with the treatment of this disease. They refer a possibility to accelerate the healing with active approach using the combination of surgical debridement with a suitable local therapeutic witch results in better healing shortening the interval between the drainage of the pus and the secondary wound suture, bettering the cosmetic look of the scar and the earlier start of postoperative chemo/radiotherapy.

Lupus nephritis in Lebanon.

This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (i.v.) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse i.v. steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.

[Myogenic tumors of the digestive tract]. / Myogenní nádory trávicího traktu.

BACKGROUND: Myogenic tumours of the digestive tract are not very frequent. Most often they are found in the stomach, less frequently in the colon and rectum. Many are symptom-free and are an incidental finding on examination or surgery. Treatment is surgical and the type and extent depends on the type, size, site and spread of the tumour. The objective of the submitted paper is to present a group of patients and to confront the findings with those of other authors. METHODS AND RESULTS: In the course of ten years (1992-1996) the authors diagnosed a myogenic tumour of the digestive tract only in 10 patients. Seven patients were males, three females, mean age 64 years (range 46-89 years). The most frequent symptoms were haemorrhage into the GI tract (6x), abdominal pain (4x), palpable resistance in the abdomen (2x), subileus (1x). Most frequently the stomach was affected (7x) and the small intestine (3x). From the histological aspect the tumour was qualified as benign only 3x (site stomach, leiomyoma). Seven times the tumour was malignant (4x stomach: leiomyoblastoma, 3x small intestine: leiomyosarcoma). Five times surgery was curative, 3x palliative, 2x only explorative. At present only three patients with a benign tumour survive. CONCLUSIONS: Myogenic tumours of the GI tract are relatively rare, preoperative diagnosis is an exception. The clinical picture is non-pathognomic. The only effective therapeutic procedure is surgery: survival depends on the type of tumour.

Expression of interferon-inducible Mx-proteins in patients with IgA nephropathy or Henoch-Schönlein purpura.

Both viral infections and dysregulated cytokine synthesis have been implicated in the pathogenesis of immunoglobulin A nephropathy (IgAN) and Henoch-Schönlein purpura (HSP). Mx proteins are specifically induced by type I interferons (IFN-alpha, -beta, -omega) and are very sensitive in detecting, for example, virus-induced, in vivo production of IFN-alpha/-beta, because the biological half-life of Mx (approximately 3 days) markedly exceeds that of IFN-alpha/-beta (20 to 90 minutes). Mx concentrations in leukocytes were measured by enzyme-linked immunosorbent assay (ELISA) in 79 blood samples of 35 patients with IgAN and five with HSP. No patient showed symptoms of infections at the time of the examination. Compared with normal leukocyte Mx concentrations (<2 mU/1,000 leukocytes), only 3 of 79 samples of IgAN/HSP patients showed mildly elevated Mx concentrations (range, 2.2 to 3 mU/1,000 leukocytes). By contrast, patients with increased endogenous IFN production (lupus erythematosus) or patients treated with IFN-alpha2 showed leukocyte Mx concentrations of up to 35 mU/1,000 leukocytes. In patients with IgAN and HSP, leukocyte Mx concentrations were not correlated with various clinical parameters. Immunohistochemically, no renal Mx expression could be detected in eight renal biopsy specimens of patients with various stages of IgAN, whereas control specimens (skin of patients treated with IFN-alpha2) showed abundant cellular Mx expression. Furthermore, human mesangial cells in vitro showed marked Mx production after exposure to IFN-alpha or IFN-beta. We conclude that, in patients with IgAN/HSP, no evidence of an activation or dysregulation of the type I interferon system can be detected.

Managing diabetes mellitus in a Lebanese primary care centre. Working towards change.

OBJECTIVES: Demand for medical care in Lebanon is dominated by diseases, such as diabetes. Quality of documentation of care given to these patients in a primary care centre, prior to and after introducing a diabetes initiative (DI) is reported. METHODS: Chart audit of diabetic patients attending an inner city health centre in Beirut, during 1/6/94-30/8/96 was conducted. DI was introduced in 1/1/97, and audit repeated six months later. RESULTS: First and second audits identified 213 and 162 patients respectively. Audit I showed poor recording for almost all parameters; example: family history (3%), smoking status (11%), hypertension (9%), dyslipidaemia (4%), BMI (nil), blood pressure (46%), foot exam (16%), HbA1c (nil), serum cholesterol and triglyceride (27%) and urine analysis (12%). Audit II revealed an improvement in the recording of most parameters, risk factors such as: smoking status, hypertension, hyperlipidaemia (98-99%), physical examination: BMI (39%), foot and peripheral circulation (91-92%), blood pressure (87%). Over half the patients had undergone a complete metabolic workup. CONCLUSION: Over the short period of time, there appears to have been an important improvement in the documentation of medical care for these diabetic patients. Effects of this change in terms of clinical outcomes is currently being assessed.

Intracellular staining of Mx proteins in cells from peripheral blood, bone marrow and skin.

AIM/BACKGROUND: The Mx proteins are known to be specifically and dose dependently induced in mononuclear cells (MNC) by type I interferons (IFN). The aim of this study was to establish a staining method for the human intracellular Mx proteins, MxA and MxB, in leucocytes and bone marrow and skin cells. METHODS: Several monoclonal antibodies directed against the MxA and MxB proteins were generated. These antibodies were used to stain Mx proteins in both frozen and paraffin wax sections using the standard alkaline phosphatase anti-alkaline phosphatase (APAAP) method. RESULTS: Granulocytes, monocytes and lymphocytes extracted from freshly collected blood from 21 healthy subjects did not stain. After incubating MNC from these subjects with IFN alpha 2b for 48 hours, Mx proteins were detected in monocytes and lymphocytes. Within two days of starting treatment with subcutaneous IFN alpha 2b, granulocytes, monocytes and lymphocytes of 16 patients with cancer stained strongly for Mx proteins. The intensity of staining was correlated with the Mx content of whole blood measured using a specific ELISA. Prior to IFN treatment, cells from bone marrow and skin tissue specimens were negative for Mx proteins with the exception of endothelial cells. During treatment with IFN alpha 2b, nearly all cells from bone marrow and skin stained intensely. CONCLUSIONS: These new monoclonal antibodies facilitate the detection of Mx positive cells in peripheral blood and in frozen or paraffin wax specimens. The advantage of this staining method is that individual cells which have responded to viruses or biologically active IFN alpha, beta or omega can be identified.