Biochemical modulation of cell energy by 2-deoxyglucose and malonate in 7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats.

The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5'-triphosphate) and oxidative stress in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II-V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.

Effects of individually optimized rocker midsoles and self-adjusting insoles on dynamic stability in persons with diabetes mellitus and neuropathy.

BACKGROUND: Persons with diabetic peripheral neuropathy (DPN) may face challenges such as balance issues due to reduced somatosensory feedback and an increased risk of developing diabetic foot ulcers (DFUs) due to increased plantar pressure. Pressure reducing footwear is thought to further impair balance. We introduced 3D-printed rocker midsoles and self-adjusting insoles that are able to reduce elevated plantar pressure values and aimed to prevent balance deterioration. However, their effect on the balance during walking (dynamic stability) is not analyzed yet. RESEARCH QUESTION: Is dynamic stability of persons with DPN impaired compared to healthy individuals and what is the effect of the 3D-printed rocker midsoles and self-adjusting insoles on the dynamic stability in this population? METHODS: Dynamic stability, specifically the margins of stability (MOS) in the anterior-posterior (AP) and medio-lateral (ML) direction, was measured in ten healthy and nineteen persons with DPN. Independent-samples t-test was applied to analyze the difference in the MOS between groups. One-way repeated measures analyses of variance (ANOVA) was conducted to test the difference between the therapeutic footwear combinations within the DPN group. RESULTS: There is no significant difference between the healthy and DPN group in MOS-AP. MOS-ML is significantly larger in DPN compared to the healthy participants. Using the self-adjusting insole shows a significantly lower (negative) MOS-AP compared to when using a rocker shoe within the DPN group. SIGNIFICANCE: This study provides valuable information on whether DPN and our therapeutic footwear have a negative effect on the dynamic stability. DPN does not have a negative effect on dynamic stability in the AP direction. For the ML direction, DPN seems to cause larger MOS-ML by likely using a compensation strategy (e.g., wider steps) while our experimental footwear does not further impair the MOS-ML.

Effects of individually optimized rocker midsoles and self-adjusting insoles on plantar pressure in persons with diabetes mellitus and loss of protective sensation.

INTRODUCTION: Rocker shoes and insoles reduce peak pressure (PP) in persons with diabetes (DM) and loss of protective sensation (LOPS). However, they are handmade, leading to inconsistent effectiveness. If foot structure changes over time, high PP-locations also change. To address this, individualized algorithm based 3D-printed rockers and self-adjusting pressure-reducing insoles are applied. METHODS: PP across seven foot regions was analyzed in 21 persons with DM and LOPS. Regions with PP < 200 kPa were considered not at risk (RnoR); regions with PP ≥ 200 kPa at risk (RaR). The aim was to offload RaR, while remaining PP < 200 kPa in RnoR. RESULTS: Individualized rockers and self-adjusting insoles combined successfully reduce PP < 200 kPa (on average 24 % - 48 %) in all feet with toes, central and lateral forefoot identified as RaR. Same intervention reduces PP in 68 % of the feet with medial forefoot identified as RaR. With the heel as RaR, no intervention reduces PP successfully in all feet. CONCLUSIONS: Individualized 3D-printed rockers combined with self-adjusting insoles reduce PP (< 200 kPa) in toes, central and lateral forefoot, but not in heels. Alternative insoles with medial arch support, heel cup and compliant midsole materials might enhance success rate across entire foot.

Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction.

INTRODUCTION: Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP). AIM: Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED). METHODS: One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes. MAIN OUTCOME MEASURES: Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кß, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP). RESULTS: Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кß, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кß, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups. CONCLUSION: Water-soluble curcumin could enhance erectile function with more effectiveness and with more prolonged duration of action.

[Hepatitis B prevalence and risk factors in Morocco]. / Prévalence de l'infection par le virus de l'hépatite B et l'évaluation des facteurs de risque au Maroc.

AIM: The aim of this study was to determine the prevalence of hepatitis B and the risk factors in Morocco. STUDY DESIGN: A total number of 16,634 individuals were screened for HBsAg using the Murex HBsAg Version 3 assay and were interviewed using a structured standard questionnaire to collect information about risk factor. RESULTS: Two hundred seventy-six subjects were positive for HBsAg, the prevalence of HBV infection was 1.66%. Using a structured standard questionnaire we reported that sexual behaviours (43.84%) are among the main risk factors for HBV transmission. CONCLUSION: This study indicates that the prevalence of HBsAg in Morocco is currently estimated at 1.66% in the active population. The risk factors for HBV infection identified here indicate that prevention is the most cost-effective method for successfully controlling HBV infection, so vaccination remains the best way to control this infection and its related complications.

Red blood cell derived extracellular vesicles during the process of autologous blood doping.

The purpose of this pilot study was to investigate the effects of the transfusion of one erythrocyte concentrate on the number of circulating red blood cell extracellular vesicles (RBC-EVs) and their clearance time. Six, healthy volunteers donated their blood and were transfused with their RBC concentrate after 35-36 days of storage. One K2 EDTA and one serum sample were collected before donation, at four timepoints after donation and at another six timepoints after transfusion. RBC-EVs were analyzed on a Cytek Aurora flow cytometer. A highly significant increase (p < 0.001) of RBC-EVs from an average of 60.1 ± 19.8 (103 /µL) at baseline to 179.3 ± 84.7 (103 /µL) in the first 1-3 h after transfusion could be observed. Individual differences in the response to transfusion became apparent with one volunteer showing no increase and another an increased concentration at one timepoint after donation due to an influenza infection. We concluded that in an individualized passport approach, increased RBC-EVs might be considered as additional evidence when interpreting suspicious Athletes Biological Passport (ABPs) but for this additional research related to sample collection and transport processes as well as method development and harmonization would be necessary.

Prevalence of Toxoplasma gondii infection in diabetic patients in Makkah AL Mukarramah, Saudi Arabia.

Toxoplasmosis is a parasitic and zoonotic disease caused by Toxoplasma gondii. The disease has worldwide distribution and all people maybe under the risk of getting infected by the parasite. The overall aim of this research was to detect the prevalence rate of antiToxoplasma gondii IgM and IgG among diabetic patients in Makkah, Saudi Arabia. Blood samples were collected from diabetic patients. Toxo IgM and IgG combo rapid test cassette were used to screen the samples, and the results were confirmed by using Enzyme-Linked Immunosorbent Assay (ELISA) to detect anti-IgM and anti- IgG antibodies on the plasma of 90 diabetic patients who attended the mobile clinic or AL Noor hospital in Makkah area. The subject was asked to complete a structured questionnaire. The questionnaire data and serological results were analyzed by using SPSS 20. Chi-square was used to compare different variables. Out of 90 samples, 39 (43.3%) were positive to anti-Toxoplasma gondii IgG wherein 33 (36.6%) of them were male and 6 (6.7%) were female. The age ranged between 13-85 years with the mean of 49.9 years. The study found that there were statistical differences between the age groups with higher prevalence in the 50-65 years age group. Detection of IgM against T. gondii gave negative results. The results of the study indicate that latent T. gondii in diabetic patient are relatively high especially among the 50-65 age group. There were significant associated between direct contact with a cat and infection by T. gondii (p<0.05).

Managing femoral head osteonecrosis in patients with sickle cell disease.

With an increasing number of people immigrating between different countries, sickle cell disease (SCD) is spreading all over the world. Due to improved health care, the life span of SCD patients has increased and many of them live to adulthood and middle-age. Osteonecrosis of the femoral head is one of the most common musculo-skeletal problems in SCD patients. Once osteonecrosis starts in the femoral head, it can progress from early to late stages in just a few years. Managing osteonecrosis of the femoral head in young-adults is a challenging problem and, in many situations, it requires major surgical procedures. In the early stages of the disease it is advisable to treat it by femoral head preserving procedures. In advanced stages, hip replacement arthroplasty (HPA) is indicated. In SCD patients, the incidence of operative complications and failure rates are higher than that for osteonecrosis due to other causes. Understanding the problems of SCD patients; appropriate diagnosis, prognosis, implications of the procedure performed and taking the necessary precautions, can reduce the complications and delay the failure of surgical procedures.

Testicular sperm aspiration (TESA) for infertile couples with severe or complete asthenozoospermia.

The aim of the study was to evaluate reproductive outcomes in a cohort of infertile couples with severe and complete asthenozoospermia undergoing TESA (testicular sperm aspiration) with ICSI. We conducted a retrospective study of 28 couples with complete or severe asthenozoospermia who underwent TESA between January 2010 and December 2015. We compared TESA-ICSI outcomes of these couples to ejaculate ICSI outcomes of 40 couples with severe asthenozoospermia treated during the same time period at our institution. Couples with female factor infertility and/or female aged ≥39 were excluded. Sperm retrieval rates and ICSI outcomes [(MII oocytes, fertilization rate, good embryo rate (transferred and frozen), couples with embryo transfer (per cycle started), clinical pregnancy (per embryo transfer)] were recorded. Patients were grouped based on whether they had ejaculated (Ej-group) or testicular (TESA-group) spermatozoa used. Testicular sperm patients were further classified based on whether they had complete asthenozoospermia (0% total motility) (Tc-group) or severe asthenozoospermia (≤1% progressive motility) (Ts-group). Mean (±SD) male and female ages were 36 ± 6 and 32 ± 4, respectively. Sperm recovery by testicular sperm aspiration (TESA) was successful in 100% (28/28) of the men. The overall clinical pregnancy rate (CPR) per cycle started was 34% (23/68) with a mean of 1.1 ± 0.4 embryos transferred per transfer. Fertilization rates were significantly lower in TESA-group compared to Ej-group (52% vs. 67%, respectively; p = 0.001), while male age was significantly higher in TESA-group compared to Ej-group (34 ± 6 vs. 37 ± 6, respectively; p = 0.03). Moreover, female age was significantly higher in Tc-group compared to Ts-group (30 ± 4 vs. 33 ± 3, respectively; p = 0.0285). However, there were no significant difference in clinical pregnancy rate per embryo transfer in the Tc-group, Ts-group, and Ej-group (50% vs. 45% vs. 57%, respectively; p = 0.8219). The data suggest that testicular sperm-ICSI is no better than ejaculated sperm-ICSI in couples with severe or complete asthenozoospermia. Randomized, controlled trials comparing ejaculated vs. testicular spermatozoa are needed to assess the true benefit of TESA-ICSI in these couples.

Glucose- and Triglyceride-lowering Dietary Penta-O-galloyl-α-D-Glucose Reduces Expression of PPARγ and C/EBPα, Induces p21-Mediated G1 Phase Cell Cycle Arrest, and Inhibits Adipogenesis in 3T3-L1 Preadipocytes.

Plant polyphenols, such as hydrolysable tannins, are present in the human diet and known to exhibit anti-diabetic and anti-obesity activity. We previously reported that the representative hydrolysable tannin compound α-penta-galloyl-glucose (α-PGG) is a small molecule insulin mimetic that, like insulin, binds to insulin receptor (IR) and activates the IR-Akt-GLUT4 signaling pathway to trigger glucose transport and reduce blood glucose levels in db/db and ob/ob diabetic mice. However, its effects on adipogenesis and lipid metabolism were not known. In this study, high fat diet (HFD)-induced diabetic and obese mice were treated with α-PGG to determine its effects on blood glucose and triglycerides. 3T3-L1 preadipocytes were used as a cell model for identifying the anti-adipogenic activity of α-PGG at molecular and cellular levels as a first step in elucidating the mechanism of action of the compound. In vivo, oral administration of α-PGG significantly reduced levels of blood glucose, triglyceride, and insulin in HFD-induced diabetic/obese mice (P<0.05). In vitro, α-PGG inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes. α-PGG suppressed the expression of positive adipogenic factors PPARγ C/EBPα and mTOR and augmented the negative adipogenic factor Pref-1. Furthermore, α-PGG induced upregulation of p21 and G1 phase cell cycle arrest. In contrast, adipogenic signaling pathways mediated by insulin, the cAMP response element binding protein (CREB) and glucocorticoid receptor (GR), were not inhibited. RNAi knockdown of p21 led to a 4-fold increase in triglyceride level in 3T3-L1 preadipocytes treated with MDI and α-PGG compared to regular preadipocytes. These results indicate, for the first time, that α-PGG is blood triglyceride- and glucose-lowering in HFD-induced obese and diabetic mice. It selectively inhibited some but not all major adipogenic pathways as well as the mTOR-p21-mediated cell cycle regulatory pathway. It is very likely that these apparently diverse but coordinated activities together inhibited adipogenesis. These results expand our knowledge on how PGG works in adipocytes and further confirm that α-PGG functions as an orally-deliverable natural insulin mimetic with adipogenetic modulatory functions.

Quantitative assessment of smooth pursuit gain and catch-up saccades in schizophrenia and affective disorders.

The smooth pursuit responses to 5 degrees and 20 degrees/sec constant-velocity stimuli were recorded from 23 patients with schizophrenia, 16 affective disorder patients, and 21 normals using low-noise infrared oculography. Pursuit gain, catch-up saccade (CUS) rate and amplitude, and their interrelationships were examined. Gain in the schizophrenic patients was reduced only at 20 degrees/sec, but for both patient groups, CUS rate at 5 degrees/sec was significantly lower than in normals. Using CUS rate at 20 degrees/sec, the patient groups could be distinguished from each other (the rate for schizophrenic patients being highest, and the rate for affectives the lowest) but neither differed significantly from normals. The diagnostic groups did not differ significantly in mean CUS amplitude, although there was a trend for patients to have larger saccades. Gain-CUS rate correlation was strong in normals but reduced or absent in both patient groups. These results indicate that the ocular motor systems of patients with schizophrenia and affective disorders process eye position error abnormally.

Saccadic intrusions into smooth pursuit in patients with schizophrenia or affective disorder and normal controls.

Two types of saccadic intrusions into smooth pursuit eye tracking, anticipatory saccades (AS), and square wave jerks (SWJ), were measured in 23 patients with schizophrenia, 16 patients with affective disorder, and 21 normal controls. Constant velocity (5 degrees and 20 degrees/sec) predictable targets were employed. High resolution infrared oculography was employed to record eye movements. Although most subjects had at least one SWJ, there were no significant group differences, and the highest individual rates of SWJ were seen in the normal control group. On the other hand, AS were never seen in normals, but were present in 25%-44% of patients with either schizophrenia or affective disorder. Both patient groups had significantly more AS than controls, but the two patient groups were not significantly different.

Increased expression of a hemimethylated oriC binding protein, SeqA, in an aphA mutant.

In Escherichia coli, the origin of DNA replication, oriC, becomes transiently hemimethylated at the GATC sequences immediately after initiation of replication and this hemimethylated state is prolonged because of its sequestration by a fraction of outer membrane. This sequestration is dependent on a hemimethylated oriC binding protein such as SeqA. We previously isolated a clone of phage lambda gt11 called hobH, producing a LacZ fusion protein which recognizes hemimethylated oriC DNA. Very recently, Thaller et al. (FEMS Microbiol. Lett. 146 (1997) 191-198) found that the same DNA segment encodes a non-specific acid phosphatase, and named the gene aphA. We show here that the interruption of the aphA reading frame by kanamycin resistance gene insertion, abolishes acid phosphatase (NAP) activity. Interestingly, in the membrane of the null mutant, the amount of SeqA protein is about six times higher than that in the parental strain, suggesting the existence of a regulatory mechanism between SeqA and NAP expression.

Indium-111 monoclonal anti-myosin antibody in assessing skeletal muscle damage in trauma.

Accurate assessment of the severity of soft tissue damage particularly skeletal muscle associated with fractures in trauma patients is important in determining the plan of management and prognosis. We used Indium-111 labelled anti-myosin to determine the extent of skeletal muscle injury in five patients involved in traumatic accidents. We found abnormal uptake in all 20 sites of muscle injury in four patients, 13 at the sites of fractures and seven away from fracture sites. There was good correlation between the degree of uptake and the extent of muscle injury. No uptake was seen in a case with no fracture and no muscle injury. At surgery this case proved to be haemarthrosis of the left knee. Indium-111 anti-myosin scanning is a potentially sensitive and useful technique in assessing extent of acute muscle injury in trauma patients.

Role of thallium-201 in the diagnosis of solitary bone lesions.

Thallium-201 is known to accumulate in malignant tumours. In this work we are evaluating the role of thallium in differentiating benign from malignant solitary bone lesions in 28 patients with solitary bone lesions on 99Tcm-MDP bone scans. Lesions' uptake of 201Tl was evaluated using visual assessment and lesion to background ratio. We found significant uptake with a mean lesion to background ratio of 4.27 in malignant lesions and no or faint uptake with a mean lesion to background ratio of 1.37 in benign lesions.

Large saccular aneurysm and A-V fistula of the brachial vessels.

This paper reports a 39-year-old patient who developed an unusually large saccular false aneurysm and A-V fistula of the brachial vessels following a neglected penetrating wound. Rapid enlargement to 15 cm appeared after one year and the aneurysm was then stable for the six months prior to operative repair. The aneurysm was excised and lateral closure of the vessels restored continuity with uneventful recovery.

Canine leishmaniasis due to Leishmania infantum MON-1 in northern Morocco.

A seroprevalence study of canine leishmaniasis was carried out in five provinces in northern Morocco: Taounate, Al Hoceima, Zouagha Moulay Yacoub, Chefchaouen and Ouezzane. 55 localities have been concerned and a total of 1,013 dogs were screened, which represents almost 100% of the canine census. Of the screened dogs: 87 showed antibody titer > or = 100 when tested by IFAT (seroprevalence of 8.6%) and were distributed in 83 asymptomatics (without clinical symptoms) and four symptomatics (with one or several symptoms of leishmaniasis) with important variations according to the locality. Relative frequency of asymptomatic dogs was observed (8.2%), and the seroprevalence increased in middle altitude (500 m < altitude < 1,000 m) and high altitude (> or = 1,000 m). Parasites isolated from dogs were identified as L. infantum MON-1 by isoenzyme profile and Rsal digestion.

Novel quinuclidinone derivatives induce apoptosis in lung cancer via sphingomyelinase pathways.

We previously reported novel quinuclidinone analogs which induced apoptosis in lung and breast cancer cells. In this study, we designed and synthesized novel quinuclidinone analogs that showed cytotoxicity in lung cancer cells. The effects of these analogs were studied in H1299 human large cell lung carcinoma cells that are null for p53 and normal lung epithelial cell lines (NL-20). The effects of the analogs were investigated by MTT assay, ELISA based apoptotic assay, TUNEL assay, sphingomylinase activity, flow cytometry and western blot analysis. Our data indicated that derivatives 4 and 6 decreased cell proliferation and induced apoptosis in H1299 cells more than NL-20 cells. Derivatives 4 and 6 reduced percent of cells in G2/M phase in H1299 cells more than NL-20 cells and these results were confirmed by increased expression levels of cyclin E. Furthermore, derivatives 4 and 6 increased sphingomyelinase activity, caspase-8, and caspase-9 and JNK-1 expression level in H1299. Additionally, derivatives 4 and 6 induced Procaspase-3, PARP-1 cleavage, and increased caspase-3 activity. All these results confirm that our quinuclidinone derivatives provoke cytotoxicity in lung cancer cells through the interplay of key apoptosis molecules in different compartments of the cell beginning with an increase in sphingomyelinase activity.

Measurement of radon diffusion length in thin membranes.

Building regulations in Israel require the insulating of buildings against radon (222)Rn penetration from soil. In radon-prone areas membranes stretched between the soil and the building foundation are used, together with sealing other possible penetration routes. Designing the radon mitigation procedure requires checking that all sealing materials are practically, radon tight, having a thickness of at least three times the radon diffusion length. In this work, a very simple technique to evaluate the radon diffusion length in thin membranes, using a radon source of known activity and an activated charcoal canister as radon detector is presented. The theoretical formalism and measurement results for polyethylene membranes of different densities obtained in a recent comparison exercise are presented.