Infection with Plasmodium chabaudi diminishes plasma immune complexes and ameliorates the histopathological alterations in different organs of female BWF1 lupus mice.

OBJECTIVE: To determine the effect of Plasmodium chabaudi infection on the plasma level of circulating immune complexes (CICs), haemoglobin (Hb) content, urine profile, and histological features of female BWF1 mice, the murine model of systemic lupus erythematosus (SLE). MATERIALS AND METHODS: A total of 30 female BWF1 lupus mice were randomly divided into three groups as follows: group (I) control group (P. chabaudi uninfected); group (II) lupus mice infected with live P. chabaudi; group (III) lupus mice infected with irradiated P. chabaudi. Urine samples were daily collected from the second week-post infection. Mice from the three groups were killed at day 14 post-infection and heparinized blood was collected for further haemoglobin contents and plasma analysis. Paraffin-embedded kidney, liver, lung, heart, brain, ovary and skin tissues were stained with Hematoxylin and Eosin (H&E) and examined under light microscope. RESULTS: Our results reveal that infection of lupus mice with live P. chabaudi was associated with an increase in urinary Hb and a decrease in plasma Hb and CIC levels. Interestingly, infection of lupus mice with live P. chabaudi ameliorates the histopathological alterations mediated by lupus disease in kidney tissues. Although no parasite sequestration was observed in any of the investigated organs, P. chabaudi pigment deposition was observed in the liver of both live and irradiated P. chabaudi infected groups. CONCLUSIONS: This study in lupus prone BWF1 mice indicated that gamma-irradiated P. chabaudi infection has the desired lupus ameliorating effect without negative effects of malaria which assist the understanding of different responses to plasmodium sp. infection in human lupus patients.

Differences in prostate cancer detection between Canadian and Saudi populations

Few studies have addressed racial differences in prostate cancer (PCa) detection between Western and Arabian countries, although PCa has a significantly lower prevalence in Arabic populations compared to Western populations. Therefore, an explanation of this difference is lacking. Serum prostate-specific antigen (PSA) is a valuable marker used to select patients who should undergo prostate biopsies, although the manner in which it is used may require adjustments based on the ethnic population in question. We investigated racial differences in the PCa detection rate between Canadian and Saudi populations. A retrospective analysis was performed of data collected prospectively over 5 consecutive years in urology clinics at the McGill University Health Center (MUHC) and King Saud University Hospital (KSUH). Men who had high (>4'ng/mL) or rising PSA levels and a negative digital rectal examination were eligible. A total of 1403 Canadian and 414 Saudi patients were evaluated for the study; 717 and 158 men, median age 64 and 68 years, were included in the MUHC and KSUH cohorts, respectively, P<0.0001). Median serum PSA, prostate volume, and PSA density values were 6.1'ng/mL, 47.3 g, and 0.12'ng·mL−1·g−1, respectively, for MUHC patients and 5.2'ng/mL, 64.5'g, and 0.08'ng·mL−1·g−1, respectively, for KSUH patients (P<0.0001, t-test followed by one-way ANOVA). In addition, the KSUH group had a significantly lower PCa detection rate among patients younger than 60 years of age and with PSA values <10'ng/mL.

Differences in prostate cancer detection between Canadian and Saudi populations.

Few studies have addressed racial differences in prostate cancer (PCa) detection between Western and Arabian countries, although PCa has a significantly lower prevalence in Arabic populations compared to Western populations. Therefore, an explanation of this difference is lacking. Serum prostate-specific antigen (PSA) is a valuable marker used to select patients who should undergo prostate biopsies, although the manner in which it is used may require adjustments based on the ethnic population in question. We investigated racial differences in the PCa detection rate between Canadian and Saudi populations. A retrospective analysis was performed of data collected prospectively over 5 consecutive years in urology clinics at the McGill University Health Center (MUHC) and King Saud University Hospital (KSUH). Men who had high (>4'ng/mL) or rising PSA levels and a negative digital rectal examination were eligible. A total of 1403 Canadian and 414 Saudi patients were evaluated for the study; 717 and 158 men, median age 64 and 68 years, were included in the MUHC and KSUH cohorts, respectively, P<0.0001). Median serum PSA, prostate volume, and PSA density values were 6.1'ng/mL, 47.3 g, and 0.12'ng · mL(-1) · g(-1), respectively, for MUHC patients and 5.2'ng/mL, 64.5'g, and 0.08'ng · mL(-1) · g(-1), respectively, for KSUH patients (P<0.0001, t-test followed by one-way ANOVA). In addition, the KSUH group had a significantly lower PCa detection rate among patients younger than 60 years of age and with PSA values <10'ng/mL.

Changes in placental size during Ramadan.

BACKGROUND: Placental growth responds to maternal influences. Ramadan is an annual period of day-time fasting during which people in Saudi Arabia, including pregnant women, change their diets and physical activity. Little is known about the effects of this altered lifestyle on placental development. METHODS: We studied the birth records of 7083 babies born over a four-year period to Saudi nationals in Unizah, a small city 350km to the north of Riyadh, the capital city of Saudi Arabia. The records included birth weight, placental weight and gestational age. RESULTS: Mean birth weight was similar to European values but the mean placental weight and ratio of placental weight to birth weight were lower. Among babies who were in the second or third trimester of gestation during Ramadan the mean placental weight and ratio were below those of babies who were not in utero during Ramadan. Among boys the mean placental ratios were 14.4 percent (second trimester) and 14.5 percent (third trimester) compared with 14.9 percent (p=<0.001 and 0.002). The corresponding figures for girls were 14.8 and 14.6 percent compared with 15.1 percent (p=0.02 and <0.001). CONCLUSIONS: In Saudi Arabia placentas respond to mothers' limited ability to deliver nutrients to them. Placental growth slows but efficiency is increased so that fetal growth is sustained, albeit with a reduced reserve capacity. The lifestyle changes associated with Ramadan further slow placental growth. Ramadan may influence placental growth through dietary changes other than day-time fasting. Changes in placental growth during Ramadan could be associated with altered fetal programming, and may therefore have long-term implications for the health of the next generation.

HLA-G and its relation to proliferation index in detection and monitoring breast cancer patients.

Recent studies indicate an ectopic upregulation of the human leukocyte antigen G (HLA-G) in tumor cells that may favor their escape from antitumor immune responses. The role of HLA-G in breast cancer has not been defined. Other studies showed that HLA-G transcription may be silenced by epigenetic mechanisms or activated by stress. This work aimed to clarify the expression of HLA-G protein, estimate the possible prognostic role of HLA-G expression and identify if this expression is linked to the DNA index (DI) and S phase fraction (SPF) in breast cancer. HLA-G protein expression and the DNA parameters were studied by flow cytometry and serum secreted HLA-G (sHLA-G) levels were detected by enzyme-linked immunosorbent assay (ELISA) in 45 breast cancer patients and 40 female blood donors as healthy donors. Surface HLA-G was expressed on 40% and the cytoplasmic pattern with no membrane association in 24.4% of the malignant specimens. There was an increased serum sHLA-G level in patients as compared with controls. There were negative correlations between cytoplasmic HLA-G and both DI and SPF and between preoperative sHLA-G and SPF with no relations with patients' clinical outcome. We cannot establish that HLA-G protein can be a useful prognostic marker, but sHLA-G may be used as a tumor marker in breast cancer patients.

Human melanoma cells release soluble and functional receptors.

Cytokines play important roles in the growth and growth arrest of cancer cells. IL-13 via an IL-4R alpha/IL-13R alpha 1 heterocomplex receptor inhibits the growth of renal cell carcinoma cells (RCC). However, it does not inhibit the growth of glioblastoma cells that express the IL-13R alpha 2 chain. In the present studies we investigated whether melanoma cells express IL-13R alpha 1 and IL-13R alpha 2 chains as well as whether they respond to IL-13. Membrane IL13R alpha 2 was co-expressed with IL-4R alpha and IL-13R alpha 1 chains in three of six tested melanoma cell lines. Furthermore, the IL-13R alpha 2 positive cell lines, release a soluble form of IL-13R alpha 2, specifically under IL-13 but not IL-4 stimulation. The release of soluble IL-13R alpha 2 was inhibited by various metalloproteinase inhibitors and EDTA inhibits the biological response to IL-13.

Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels.

Capillaries in the retina are more susceptible to develop microvascular lesions in diabetes than capillaries in the embryologically similar cerebral cortex. Because available evidence implicates hyperglycemia in the pathogenesis of diabetic retinopathy, differences in glucose transport into the retina and brain might contribute to this observed tissue difference in susceptibility to diabetes-induced microvascular disease. Thus, we compared levels of GLUT1 and GLUT3 expression in the retina, cerebrum, and their respective microvessels by Western blot analysis. In nondiabetic animals, the content of GLUT1 protein in retina and its microvessels was multifold greater than that of cerebral cortex gray matter and its microvessels. Streptozotocin-induced diabetes of a 2-week or 2-month duration reduced GLUT1 expression in the retina and its microvasculature by approximately 50%, but it resulted in no reduction in GLUT1 expression in cerebrum or its microvessels. The density of capillaries in retinas of diabetic animals did not change from normal, and so the observed decrease in GLUT1 expression in the retina and retinal capillaries of diabetic animals cannot be attributed to fewer vessels. Despite the diabetes-induced reduction of GLUT1 expression in retina, neural retina of diabetic rats still possessed more GLUT1 than the cerebrum. Retinal pigment epithelium (RPE) possessed more GLUT1 than neural retina or its microvessels, and expression of the transporter in the RPE was not affected by diabetes. GLUT3 levels were greater in cerebral gray matter than in retina, and they were unaffected by diabetes in either tissue. The effect of diabetes on GLUT1 expression differs between retina and cerebral cortex, suggesting that glucose transport is regulated differently in these embryologically similar tissues. Because diabetes results in downregulation of GLUT1 expression in retinal microvessels, but not in RPE, the fraction of the glucose entering the retina in diabetes is likely to be greater across the RPE than across the retinal vasculature.

Glut1 and glut3 expression, but not capillary density, is increased by cobalt chloride in rat cerebrum and retina.

Treatment of rats with cobalt chloride [Co(II)], an agent that stimulates the expression of a set of hypoxia-responsive genes, for 10-12 days resulted in 1.45- and 1.40-fold increases in the content of Glut1 mRNA and Glut1 in cerebral gray matter, respectively (P<0. 05 for both changes). The increase in Glut1 content was associated with a significant increase in the content of Glut1 staining in microvessels isolated from cerebral gray matter, and in the intensity of Glut1 in microvessels of the frontal lobe and hippocampus assessed by immunohistochemistry. The abundance of Glut3 in cerebrum of Co(II)-treated rats also increased by 1.3-fold (P<0. 05), but the increase was not associated with a change in the content of Glut3 mRNA. In retina, treatment with Co(II) resulted in 2.48- and 1.23-fold increases in the content of Glut1 mRNA and Glut1 protein, respectively (P<0.05 for both changes); similar increases in Glut1 protein expression were observed in isolated retinal microvasculature. The content of Glut3 in retina also increased 1. 5-fold in Co(II)-treated rats (P<0.05). In addition, treatment with Co(II) resulted in a significant 2.2-fold increase in the expression of VEGF in the cerebrum. However, despite the Co(II)-induced increase in Glut1 expression in cerebral and retinal microvasculature and VEGF in cerebrum, there was no increase in the capillary density in either tissue. It is concluded that a 10-12 day exposure to Co(II), presumably acting through the hypoxia-signaling pathway, results in enhanced expression of both major glucose transporters in cerebral cortex and retina, without increasing the capillary density of either tissue.

Chronic liver disease in the Alexandria governorate, Egypt: contribution of schistosomiasis and hepatitis virus infections.

BACKGROUND/AIMS: In Egypt chronic liver disease is customarily attributed to Schistosoma mansoni infection. Anti-HCV antibodies are highly prevalent among Egyptian blood donors, yet little is known about the risk factors, pathogenicity and virological features of HCV and its association with schistosomiasis. We studied 135 adult patients with chronic liver disease living in the Alexandria governorate, mostly in rural areas of the Nile Delta. METHODS: Evaluation included abdominal ultrasonography; detection of anti-HCV antibodies and markers of HBV and HDV infection; HCV-RNA assay by 5' untranslated region nested polymerase-chain-reaction and HCV genotyping by a line probe assay; serologic (anti-soluble egg antigen, anti-SEA) and parasitological examinations for Schistosoma mansoni infection; and liver biopsy, if not contraindicated. RESULTS: Ninety-one (67%) patients had anti-HCV and 107 (85%) anti-SEA, 32 (30%) of whom excreted schistosomal eggs in stools. In addition, 21 (16%) patients had HBsAg, 86 (64%) anti-HBc and four (3%) anti-delta. Thus, many patients had evidence of multiple infections, double in 66% (anti-HCV and anti-SEA), triple in 33% (anti-HCV HBsAg and anti-SEA). Based on our diagnostic criteria, 25 (19%) patients had schistosomal portal fibrosis (anti-HCV positive in eight), 24 (18%) chronic hepatitis (anti-HCV positive in 19), 76 (56%) cirrhosis (anti-HCV positive in 58) and 10 hepatic tumors (anti-HCV positive in six). At multivariate analysis, the presence of anti-HCV was independently associated with previous parenteral anti-schistosomal therapy, a history of hematemesis and seropositivity for anti-HBc. Fifty (55%) of 91 anti-HCV positive sera had HCV-RNA, in 41 cases classified as genotype 4a. Detection of HCV-RNA was associated with a more severe liver disease and occurred less frequently in patients with a history of schistosomiasis. CONCLUSIONS: HCV infection with genotype 4a is the main cause of severe chronic liver disease in Egypt, where it is highly associated with schistosomiasis.

Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study.

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on "intent-to-treat" data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0-2), medium (3-5) and high (6-8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.

Brain stem and spinal cord impairment in Rett syndrome: somatosensory and auditory evoked responses investigations.

Six females with Rett syndrome (RS)--all seriously motor disabled with clinical symptomatology indicating not only brain but also spinal cord impairment--were investigated using auditory and somatosensory evoked responses techniques. In all patients the responses representing the pathways through the upper spinal cord were delayed suggesting an impairment of the central conduction time. The findings mean an involvement of the sub-cortical structures, the brain stem and the cervical spinal cord in the disease process. From the natural clinical course and the present findings, it is concluded that RS is also characterized by spinal cord impairment appearing with increasing age and stage of diseases.

Trigeminal dysfunction in patients with Bell's palsy.

The trigeminal function was investigated in 30 consecutive patients with acute unilateral peripheral facial palsy. The patients were tested with electrophysiological methods within 5 weeks after onset of the disease. Trigeminus-evoked potential test (TEP) disclosed trigeminal dysfunction in 47%, while the blink reflex test (BR) showed trigeminal pathology in 60% of the patients. A topographical analysis of the trigeminal system showed that 24% of the patients had BR patterns that were consistent with brainstem involvement. In 2 cases (7%), TEP was pathological though the BR test proved normal. These findings suggest a more central trigeminal affection and may demonstrate multifocal lesions. This was further underlined by the investigation of the auditory brainstem response (ABR) which indicated brainstem involvement in 28%. It is concluded that acute facial palsy is frequently a symptom of a central nervous affection.

Somatosensory evoked potentials and cerebral metabolism during cardiopulmonary bypass with special reference to hypotension induced by prostacyclin infusion.

Somatosensory evoked potentials and cerebral metabolism were studied during cardiopulmonary bypass in 41 patients undergoing coronary bypass. Twenty-two patients received prostacyclin 50 ng/kg/min during cardiopulmonary bypass for platelet protection and 19 patients served as controls. Mean arterial blood pressure in the prostacyclin group was below 30 mm Hg during the first 30 minutes of bypass, but it remained above 50 mm Hg in the control group. Central conduction time, a measure of the electrical conduction time in the central nervous system, was prolonged in both groups during bypass up to 30 minutes of rewarming. The prolongation was greater in the control group early during bypass. At 20 minutes of cardiopulmonary bypass, central conduction time was increased by 81% (standard deviation 38) of the prebypass value in the control group and by 44% (standard deviation 17) in the prostacyclin group (p less than 0.001). Arteriovenous oxygen difference across the brain was greater in the prostacyclin group early during bypass. It was 36 ml/L (standard deviation 9) in the control group and 60 ml/L (standard deviation 18) in the prostacyclin group (p less than 0.001) at 10 minutes of bypass. There was no difference between the groups in regard to glucose and lactate. We conclude that cardiopulmonary bypass with hypothermia prolongs central conduction time. The hypotension induced by prostacyclin (50 ng/kg/min) did not further impair conduction in the central nervous system.

Cortical evoked potentials obtained after stimulation of the lower urinary tract.

Cortical evoked potentials following stimulation of the lower urinary tract have been recorded in humans. Of 26 patients investigated 9 had no urinary signs or symptoms except genuine stress incontinence, while the remaining 17 had various neurogenic bladder disorders. Monopolar and bipolar stimulation of the bladder and urethra was performed using conventional and newly designed suction-type electrodes. While no cortical evoked potentials could be obtained from patients with complete transverse spinal cord lesions polyphasic cortical evoked potentials (N45, P60, N80 and P100 msec.) were recorded in response to monopolar bladder stimulation in all patients with stress incontinence. Following bipolar stimulation a response with lower amplitude and with latencies slightly divergent could be recorded. This response is assumed to be evoked only from bladder afferent nerves, while the monopolar response could include activity from adjacent structures. The most consistent pattern was recorded at the Cz site. Cortical evoked potentials following stimulation of the urethra were more difficult to evoke but they resembled those obtained after bipolar stimulation of the bladder. The method, when fully developed, may be helpful in the clinical investigation of patients affected by various neurogenic disorders of the lower urinary tract. So far, in our limited series a delayed response at P2 has been observed in patients with uninhibited neurogenic bladders.

Auditory brain stem response abnormalities in patients with Bell's palsy.

To evaluate the hypothesis of CNS involvement in Bell's palsy, the auditory brain stem responses (ABR) of 31 patients were studied. In nine of these patients ABR abnormalities were found. None of these patients showed evidence of dysfunction of the cochlear nerve. Six of the patients who had abnormal ABR were retested after they recovered from the facial paresis. Five of these patients showed persistent ABR abnormality, and one showed a normalization of the ABR. These results may be consistent with an injury at the brain stem level in some patients with Bell's palsy. The possible causative agent of a reactivation of a herpes simplex virus infection is discussed.

Cortical evoked potentials in response to trigeminus nerve stimulation in humans.

A standard technique for recording trigeminal somatosensory evoked potentials (TEP) in response to stimulation of the second branch of the trigeminus nerve is described. Thirty-six nerves of 18 apparently healthy subjects have been investigated. A characteristic polyphasic wave was repeatedly observed. It consisted mainly of a P20, N30, P40, N50 sequence of deflections. Intraindividual variations were minimal. The response pattern varied according to the positions of the recording and stimulating electrodes. The method is useful in detecting functional integrity of the afferent pathways of the 5th cranial nerve, and it can be used as a diagnostic tool for routine investigation of the trigeminus nerve.

A quantitative EEG analysis of the effects of baclofen on man.

This investigation has been directed to estimate to what extent a GABA derivative, beta-(p-chlorophenyl)-gamma-aminobutyric acid (baclofen), is active at the cortical and subcortical level. Selected nonpsychotic patients with slight depression symptoms were given 30 mg of baclofen daily for a period of 3-5 weeks. Brief Psychiatric Rating Scale and Standardized Hamilton Interview for Depression were used for clinical evaluation. EEGs were recorded prior to and at different times during treatment. An automatic analysis completed by multivariant statistics of EEG spectral values was performed. EEG changes were characterized by a significant increase of slow waves and decrease of fast activity. These results can support the view that baclofen is effective even at the highest levels of the central nervous system.

Cortical evoked potentials following stimulation of the urinary bladder in man.

Techniques are described for recording evoked potentials in humans in response to stimulation of the urinary bladder. Twenty patients with various disorders of their urinary function were investigated. Evoked cortical potentials following stimulation of the urinary bladder could be recorded from all patients except subjects with complete transverse spinal cord lesions. The response was most evident at the central site (Cz) and had its most prominent peaks at 45, 65, 82 and 102 msec. This technique may become a useful diagnostic tool in the study of neurogenic bladder dysfunctions.

[Quantitative EEG in depression (author's transl)]. / Intérêt de l'electroencéphalogramme quantitatif dans la dépression.

Evaluation of the treatment in clinical psychiatry is mostly based on the rating of mental symptoms prior and after treatment. There is an obvious need to supplement clinical observations by objective measurements. Based on EEG automatic analysis, three methods which appeared to be valuable in investigating patients with affective psychosis, are briefly reviewed. 1) The EEG drug profile, indicating changes of the EEG frequency pattern, which varies proportionally to the psychoactive properties of the drug and its metabolites. 2) The fluctuations of the vigilance level which monitor the sedative/excitatory effect of drugs. 3) The interhemispheral assymetry which is related to the intensity of depression.