Gluten-Free, Casein-Free Diet for Children with Autism Spectrum Disorder: A Case-Controlled Study.

Background and Objectives: Numerous therapeutic and dietary interventions have been examined in the last thirty years for pediatric patients diagnosed with autism spectrum disorder (ASD). Our interventional study aimed to assess the effectiveness of the gluten-free, casein-free (GFCF) diet in a cohort of Egyptian children with ASD. Materials and Methods: The present clinical trial was conducted as a prospective 12-month, open-label, case-controlled interventional study. Thirty-six ASD children who were newly diagnosed and had not taken any prior psychiatric or rehabilitation therapy were included in this study. The patients were randomly assigned into two groups: group A, which received the GFCF diet, and group B, which served as the control group and was not restricted to food containing gluten and casein for 12 months. All patients were followed up for 1 year. Results: Following the implementation of the GFCF diet in group A, significant improvements in CARS scores were observed compared to group B after 6-month and 1-year follow-up periods. Conclusions: The introduction of the GFCF diet could be helpful and promising for autistic children. Conclusive evidence regarding the effectiveness of the GFCF diet remains a subject of controversy. Nonetheless, our study contributes some evidence supporting its potential benefits for children with ASD. It is recommended that future research on the GFCF diet employ a more sophisticated research design, incorporating a consistent baseline measure that can effectively assess the therapeutic effects of these interventions for individuals with ASD.

The superior efficacy of chloroquine over buparvaquone in reducing the chronic cerebral Toxoplasma gondii cysts load and improving the ultrastructural pathology in an immunocompromised murine model.

Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 - 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.

The superior efficacy of chloroquine over buparvaquone in reducing the chronic cerebral Toxoplasma gondii cysts load and improving the ultrastructural pathology in an immunocompromised murine model

@#Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 – 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.

Efficacy of topical testosterone in management of scrotal hypoplasia and agenesis.

BACKGROUND: Scrotal hypoplasia or agenesis may posses difficulty during orchidopexy or end with social anxiety around excessively small scrotal size when compared to peers, and where there may be concerns regarding the future sexual life. OBJECTIVE: Any conservative modality applicable to ameliorate scrotal underdevelopment partially or completely will be useful either solely or before reconstructive surgery. STUDY DESIGN: Seventeen child (3-8 years) were diagnosed with bilateral scrotal hypoplasia (SH) in 5 unilateral in 7, bilateral scrotal agenesis (SA) diagnosed in 4 cases, and unilateral in one. Testicles are either undescended, ectopic, or normal. All cases managed by Testogel 1% topical testosterone for 4 weeks. Clinical assessment by measurements of the scrotal skin surface area (scrotal length multiplied by width) and scrotal corrugations counting. Inguinal and renal ultrasound done for all cases and karyotyping for cases of agenesis and cases with bilateral undescended testicles. Total and free testosterone, LH, FSH and AMH hormones were assisted before treatment, weekly and one week after therapy. Data analyzed and evaluated, difference of means used to test for statistically significant differences between scores of scrotal development. RESULTS: Free and total testosterone elevated in the 1st week of treatment, but restored to normal or higher levels in 60% of cases at the 2nd week. Satisfactory response (Increasing numbers of scrotal rugae or scrotal surface area by 30-50% above the pretreatment status) obtained in 85% and 60% of unilateral and bilateral SH, but only a partial response (10-20% increase) was gained in 40% of cases with agenesis. No major adverse effect was appreciated. DISCUSSION: Response of some cases of SH to topical testosterone indicates presence of remnants of labioscrotal folds with testosterone receptors (Bell et al., 1971) [1]. Testosterone replacement therapy can improve the signs and well-being of a hypogonadal male by restoring serum testosterone concentrations to physiologic levels. In this study the mean average testosterone concentration one week after application of testogel was 13.47 ± 2.45 and 12.12 ± 2.5 within 2nd, 4th week, and after cessation of treatment. Anti-Mullerian hormone is significantly low in 12 cases; mainly in cases of SA (P-value <0.001). CONCLUSION: Short term topical testosterone proved to be effective in a considerable percentage of cases of either bilateral or unilateral scrotal hypoplasia; with a subsequent increase in scrotal surface area and number of rugae, it may substitutes the indication for surgical reconstruction. Long term follow up is a limitation of this study.

The potential relationship between gasotransmitters and oxidative stress, inflammation and apoptosis in lead-induced hepatotoxicity in rats.

The interrelationship between gasotransmitters and oxidative stress, inflammation and apoptosis in lead-induced hepatotoxicity was investigated in this study. On prolonged exposure, lead was accumulated in liver tissue of rats and impaired liver function and structure as assessed by measurement of the serum hepatic function markers and by histopathological examination. The accumulated metal induced oxidative stress, inflammation and apoptosis in the liver. Also, it increased nitric oxide (NO) production and decreased hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in liver tissue. Decreasing of NO production by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and carbon monoxide (CO) level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of liver function and structure. Concomitantly, these agents inhibited lead intoxication-induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of HO-1 concentration and H2S level. Furthermore, concurrent treatment with these agents inhibited lead intoxication-induced increase in the protein expressions of inducible NO synthase, tumor necrosis factor-alpha, interleukin-1beta and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine-γ-lyase in the liver. NO donor, l-arginine and H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively aggravated the toxic effects of lead. These results indicate, for the first time, that there is an interrelationship between gasotransmitters and lead-induced hepatotoxicity. The ability of L-N AME, NaHS and CORM-A1 to provide protective effects against lead-induced hepatotoxicity may positively correlate, to their ability to suppress hepatic oxidative stress, nitrosative stress, inflammation and apoptosis.

Safety and Immunogenicity Evaluation of Inactivated whole-virus-SARS-COV-2 In Mice As Emerging Vaccine Development In Egypt

The current worldwide pandemic COVID-19 is causing severe human health problems, with high numbers of mortality rates and huge economic burdens that require an urgent demand for safe, and effective and vaccine development. Our study was the first trail to development and evaluation of safety and immune response to inactivated whole SARS-COV-2 virus vaccine adjuvanted with aluminium hydroxide. We used characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069 and MW250352 at GenBank that isolated from Egyptian patients SARS-CoV-2-positive. Development of the vaccine was carried out in a BSL - 3 facilities and the immunogenicity was determined in mice at two doses (55{micro}g and 100{micro}g per dose). All vaccinated mice were received a booster dose 14 days post first immunization. Our results demonstrated distinct cytopathic effect on the vero cell monolayers induced through SARS-COV-2 propagation and the viral particles were identified as Coronaviridae by transmission electron microscopy. SARS-CoV-2 was identified by RT-PCR performed on the cell culture. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless the dose concentration, with excellent safety profiles.However, no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by wild virus challenge the vaccinated mice and detection of viral replication in lung tissues. Vaccinated mice recorded complete protection from challenge infection three weeks post second dose. SARS-COV-2 replication was not observed in the lungs of mice following SARS-CoV-2 challenge, regardless of the level of serum neutralizing antibodies. This finding will support the future trials for evaluation an applicable SARS-CoV-2 vaccine candidate.

Clinical utility of transient elastography as an imaging tool to assess the short-term impact of laparoscopic sleeve gastrectomy, together with clinical and biochemical parameters and clinico-biochemical indices, on obese patients with nonalcoholic fatty liver disease: An Egyptian pilot study. / La utilidad clínica de la elastografía transitoria como una herramienta de imagenología para evaluar el impacto a corto plazo de la gastrectomía laparoscópica en manga, en conjunto con parámetros clínicos y bioquímicos e índices clínico-bioquímicos en pacientes con enfermedad de hígado graso no alcohólico: un estudio piloto egipcio.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disorder commonly attributed to fatty acid deposition that can induce hepatic necroinflammation, defined as nonalcoholic steatohepatitis (NASH). It is strongly associated with obesity. Laparoscopic sleeve gastrectomy (LSG) is a favorable surgical modality for the treatment of morbid obesity. AIM: Our study evaluated the impact of LSG on patients with NAFLD and morbid obesity, 3 months after the operation, through clinical and biochemical characteristics, clinico-biochemical indices, and imaging parameters. PATIENTS AND METHODS: Morbidly obese patients with NAFLD±NASH underwent LSG. They were thoroughly evaluated clinically (body weight, body mass index, waist circumference) and biochemically (transaminases and triglycerides), as well as through the fatty liver index (FLI), the hepatic steatosis index (HSI), and ultrasound elastography imaging studies (liver stiffness measurement [LSM] and the controlled attenuation parameter [CAP]), before and 3 months after the LSG. RESULTS: Twenty-six obese patients with NAFLD underwent LSG that resulted in a significantly high reduction in all the parameters analyzed, except for liver transaminases. CONCLUSION: LSG is considered an efficient surgical modality for the treatment of morbidly obese patients with NAFLD.

A theoretically based cross-sectional survey on the behaviors and experiences of clinical pharmacists caring for patients with chronic kidney disease.

The literature shows a lack of evidence on pharmacists contributing to chronic kidney disease services. The aim was to determine pharmacists' behaviors and experiences and perceptions of barriers and facilitators to implementation of models of care. A theoretically informed survey was developed and sent to pharmacist members of the United Kingdom renal pharmacy group. Sections included: demographics, clinical practice and prescribing practice. Questions were of various types; closed type and some open for comments. Attitudinal items on clinical/prescribing used 5-point Likert scale. Development/implementation items were derived from the Consolidated Framework for Implementation Research (CFIR). Analysis used descriptive statistics and open comments were analysed thematically. Ethical approval was granted by an academic institution. Response rate; 50% (n = 71), seven were incomplete and excluded. Respondents provided; inpatient general pharmaceutical care (n = 56, 87.5%), to those receiving dialysis (n = 54, 84.4%) and transplantation. Non-clinical roles; audits (n = 46, 71.9%), patient education (n = 31, 48.4%), only 7.8% (n = 5) doing academic research. For barrier/facilitators most strongly agreed/agreed with most CFIR items relating to clinical practice. A majority (n = 44, 68.7%) disagreed that they had sufficient time to practice clinically and 44 (68.7%) disagreed there was sufficient cover for services. For prescribing roles, 90.5% (n = 48) were currently actively prescribing. Although prescribing related CFIR items were largely positive, 39.6% (n = 19) disagreed about sufficient time to practice and 18.7% (n = 9) were neutral. Two thirds (n = 33, 68.7%) disagreed that there was sufficient cover for the prescribing. The majority of respondents provided general pharmaceutical care to dialysis and transplant patients, were confident in their abilities and tried new ways of working including independent prescribing. Many expressed that lack of resources was the main barrier to providing more advanced care. Further work is needed to explore these matters in more depth.

Cellulase Production by Fusarium graminearum and its Application in Ruminant's Diets Degradation.

BACKGROUND AND OBJECTIVE: Cellulase as a fibrolytic enzyme is a highly effective tool for agricultural waste treatments. Production of cellulase enzyme on medium of agricultural wastes by Fusarium graminearum to be used in ruminant feeding was the main objective of this study. MATERIALS AND METHODS: Impact of initial pH of growth medium, different nitrogen sources and variety of agriculture by products as a carbon sources on cellulase production have been studied. Electron microscope was used for investigate the impact of the resultant cellulase on corn stover degradation, while batch culture technique was used for investigate impact of different levels of the produced and commercial cellulases on total mixed ration digestibility by rumen microorganisms (in vitro). RESULTS: Cellulase maximum production by F. graminearum was obtained at 20% corn stover, initial pH of growth medium 5.0 and peptone as a nitrogen source. All addition levels of the produced cellulase increased dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF), cellulose and hemicellulose degradability of the treated diets, but the maximum produced cellulase efficiency% for dry matter degradability was obtained at 1200 IU kg-1 DM reached 23.19% over the control. CONCLUSION: Utilization of the produced cellulase in enrichment of the feeding value of the agricultural by-products may help in overcome of the feed gap with good impact on environment and public health.

The interrelationship between gasotransmitters and lead-induced renal toxicity in rats.

This study explored the role of gasotransmitters in lead-induced nephrotoxicity. Long-term exposure of rats to lead resulted in its accumulation in kidney. The accumulated metal impaired kidney function and structure. Lead intoxication resulted in oxidative stress, inflammation and apoptosis in kidney. In addition, it resulted in nitric oxide (NO) overproduction and decrease in hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in kidney. Inhibition of NO overproduction by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and CO level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of kidney function and structure. These agents inhibited lead-intoxication induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of H2S level and HO-1 concentration. Also, concomitant treatment with these agents inhibited lead intoxication-induced increase in protein expressions of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine- γ-lyase (CSE) in kidney. The NO donor, L-arginine and the H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively produced opposite effects and aggravated the toxic effects of lead. These results demonstrate, for the first time, that gasotransmitters play an important role in lead-induced nephrotoxicity.

Synthesis, molecular modeling studies and bronchodilation properties of nicotinonitrile containing-compounds.

Facile synthetic pathway for nicotinonitriles 5a‒o, 7a‒i was demonstrated through reaction of ketones 4a‒k, 6a‒f with ylidenemalononitrile 3 in the presence of sodium alkoxide. Meanwhile, nucleophilic attack of amines on 2-bromonicotinonitrile 9 (obtained through reaction of propenone 8 with malononitrile, followed by bromination with bromine in acetic acid) afforded 3-pyridinecarbonitriles 11a‒d. Single crystal X-ray of compound 7i reveals the monoclinic space group C2/c with 8 molecules per unit cell. Optimized structure of 7i [DFT/B3LYP, 6-31G(d,p)] shows close correlations to that of X-ray study. Compound 5l seems superior among all the synthesized analogues exhibiting bronchodilation properties about three folds potency compared to theophylline (standard reference) through pre-contracted tracheal rings with histamine standard method. Also compound 5a reveals promising observations (about two folds potency of the standard reference). Molecular modeling studies (3D-pharmacophore and 2D-QSAR) supported the observed biological properties.

Salivary MMP-9 in the detection of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour of the oral cavity. Detection of OSCC is currently based on clinical oral examination combined with histopathological evaluation of a biopsy sample. Direct contact between saliva and the oral cancer makes measurement of salivary metalloproteinase-9 (MMP-9) an attractive alternative. MATERIAL AND METHODS: In total, 30 OSCC patients and 30 healthy controls were included in this prospective study. Saliva samples from both groups were collected, centrifuged and supernatant fluid was subjected to ELISA for assessment of MMP-9. The median salivary MMP-9 values with interquartile range (IQR) of OSCC patients and the control group were statistically analysed using the Mann-Whitney U-test. The receiver operating characteristic (ROC) curve was constructed and the area under curve (AUC) was computed. RESULTS: The median absorbance MMP-9 value of the OSCC group was 0.186 (IQR= 0.158) and that of control group was 0.156 (IQR=0.102). MMP-9 was significantly increased in the OSCC patients than in the controls by +19.2% (p=0.008). Median values in patients with recurrence and in patients with primary event were 0.233 (IQR=0.299) and 0.186 (IQR=0.134) respectively. MMP-9 was significantly increased in patients with primary event (p=0.017) compared to controls by +19.2%. No significant increase of MMP-9 level was detected when comparing patients with recurrence and healthy controls (+49.4%; p=0.074). The sensitivity value of MMP-9 was 100% whereas the specificity value was 26.7% with AUC of 0.698. CONCLUSIONS: The present data indicates that the elevation of salivary levels of MMP-9 may be a useful adjunctive diagnostic tool for detection of OSCC. However, further studies are necessary to provide scientific and clinical validation.

Dose-injury relationships for cryoprotective agent injury to human chondrocytes.

Vitrification of articular cartilage (AC) could enhance tissue availability but requires high concentrations of cyroprotective agents (CPAs). This study investigated relative injuries caused by commonly used CPAs. We hypothesized that the in situ chondrocyte dose-injury relationships of five commonly used CPAs are nonlinear and that relative injuries could be determined by comparing cell death after exposure at increasing concentrations. Human AC samples were used from four patients undergoing total knee arthroplasty surgery. Seventy µm slices were exposed in a stepwise protocol to increasing concentrations of 5 CPAs (max = 8 M); dimethyl sulfoxide (Me(2)SO), glycerol (Gly), propylene glycol (PG), ethylene glycol (EG), and formamide (FM). Chondrocyte viability was determined by membrane integrity stains. Statistical analysis included t-tests and nonlinear least squares estimation methods. The dose-injury to chondrocytes relationships for all CPAs were found to be nonlinear (sigmoidal best fit). For the particular loading protocol in this study, the data identified the following CPA concentrations at which chondrocyte recoveries statistically deviated significantly from the control recovery; 1 M for Gly, 4 M for FM and PG, 6 M for Me(2)SO, and 7 M for EG. Comparison of individual means demonstrated that Gly exposure resulted in the lowest recovery, followed by PG, and then Me(2)SO, FM and EG in no specific order. The information from this study provides an order of damage to human chondrocytes in situ of commonly used CPAs for vitrification of AC and identifies threshold CPA concentrations for a stepwise loading protocol at which chondrocyte recovery is significantly decreased. In general, Gly and PG were the most damaging while DMSO and EG were among the least damaging.

Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: role of nitric oxide and oxidative stress.

Nigella sativa seed extracts and its oil have been exploited for their various health benefits. In this study, the effects of N. sativa oil on tramadol-induced tolerance and dependence and possible mechanism(s) of these effects were investigated, for the first time, in mice. Repeated administration of N. sativa oil (4 ml/kg, p.o.) along with tramadol (50mg/kg, s.c.) inhibited the development of tramadol tolerance, as measured by the hot plate test, and dependence as assessed by naloxone (5mg/kg, i.p.)-precipitated withdrawal manifestations. Concomitantly, nitric oxide overproduction and increase in brain malondialdehyde level induced by repeated administration of tramadol to mice or by administration of naloxone to tramadol-dependent mice were inhibited by co-administration of the oil. Also, the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments was inhibited by co-administration of the oil. The increase in brain glutamate level induced by both treatments was not inhibited by concurrent administration of the oil. The inhibitory effect of N. sativa oil on tramadol-induced tolerance and dependence was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine (0.25mg/kg). Also, the inhibitory effect of the oil on naloxone-induced biochemical alterations in tramadol-dependent mice was enhanced by concurrent administration of dizocilpine. Similarly, concurrent i.p. administration of the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (10mg/kg) or the antioxidant, N-acetylcysteine (50mg/kg) enhanced these inhibitory effects of N. sativa oil. On the other hand, these effects were antagonized by concurrent i.p. administration of the NO precursor, L-arginine (300 mg/kg). These results provide evidence that N. sativa oil appears to have a therapeutic potential in tramadol tolerance and dependence through blockade of NO overproduction and oxidative stress induced by the drug.

Blockade of nitric oxide overproduction and oxidative stress by Nigella sativa oil attenuates morphine-induced tolerance and dependence in mice.

The effects of Nigella sativa oil on morphine-induced tolerance and dependence in mice and possible mechanism(s) of these effects were investigated, for the first time, in this study. Repeated administration of Nigella sativa oil (4 ml/kg, p.o.) along with morphine (5 mg/kg, s.c.) attenuated the development of tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone (5 mg/kg, i.p.)-precipitated withdrawal manifestations. Concomitantly, nitric oxide overproduction and increase in brain malondialdehyde level induced by repeated administration of morphine to mice or by administration of naloxone to morphine-dependent mice were inhibited by co-administration of the oil. Also, the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments were inhibited by co-administration of the oil. The increase in brain glutamate level induced by both treatments was not inhibited by concurrent administration of the oil. The inhibitory effect of the oil on morphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine (0.25 mg/kg). Similarly, concurrent i.p. administration of the NO synthase inhibitors; L-N (G)-nitroarginine methyl ester (10 mg/kg), aminoguanidine (20 mg/kg) and 7-nitroindazole (25 mg/kg) or the antioxidant, N-acetylcysteine (50 mg/kg) enhanced this inhibitory effect of the oil. On the other hand, this effect was antagonized by concurrent i.p. administration of the nitric oxide precursor, L-arginine (300 mg/kg). These results provide evidence that Nigella sativa oil, through inhibition of morphine-induced NO overproduction and oxidative stress, appears to have a therapeutic potential in opioid tolerance and dependence.

Posterior intrafocal pinning for extension-type supracondylar fractures of the humerus in children.

We describe a method of pinning extension supracondylar fractures of the humerus in children. Following closed reduction, a posterior intrafocal wire is inserted and a second lateral wire added when needed for rotational stability. Between May 2002 and November 2005 we performed this technique in 69 consecutive patients. A single posterior wire was used in 29 cases, and two wires in 40. The mean follow-up was two years (21 to 30 months). The results were assessed according to Flynn's criteria. In the single-wire group there were 21 excellent, five good and one poor result. Two patients were lost to follow-up. In the two-wire group there were 32 excellent, two good and three poor results. Three were lost to follow-up. The poor results were due to a failure to achieve adequate reduction, fixation or both. We conclude that the intact posterior periosteal hinge can be used successfully in the clinical situation, giving results that compare well with other techniques of pinning. The posterior route offers an attractive alternative method for fixation of supracondylar fractures of the humerus in children.

ACE gene polymorphism in Egyptian children with idiopathic nephrotic syndrome.

BACKGROUND: Idiopathic nephrotic syndrome is a common renal disease in children. ACE gene insertion/deletion (I/D) polymorphism has been studied as a predictor of clinical response to steroid therapy. OBJECTIVE: To investigate the distribution of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in children with idiopathic nephrotic syndrome (INS), as well as its relation with patient's clinical response to steroid therapy. METHODS: The studied subjects included 50 children with INS compared to 20 unrelated healthy children. Each individual genotype was determined using PCR amplification of extract genomic DNA and allele distribution based on size of the PCR fragments. RESULTS: Patients with INS had a significantly higher percentage of DD genotype (p < 0.05) than the control group. D allele frequency was significantly higher in INS patients than healthy controls. CONCLUSION: Our results showed that INS is associated with a higher incidence of DD genotype, especially in non-SS patients. This data suggested that DD genotype may play a role in the clinical response to steroid. Angiotensin II may be involved in part in the response to steroid treatment in children with INS (Tab. 4, Fig. 1, Ref. 20).

Androgen receptor CAG repeat length contraction in diseased and non-diseased prostatic tissues.

To investigate contraction of CAG repeats within the androgen receptor gene (AR) as shorter CAG repeats have been implicated as a possible risk factor in prostate cancer (PCa). AR CAG repeat lengths were analyzed in DNA from microdissected diseased prostates, leukocytes from matched peripheral blood, and control non-diseased prostates. Consistently, all prostatic tissues, whether from benign or cancerous areas of diseased prostates, or from control prostates, showed multiple AR CAG repeat contractions. Germline DNA from blood leukocytes had single CAG repeat lengths in the normal range. AR CAG repeat length contraction may be involved in prostate carcinogenesis and may precede the pathological process.

Placenta percreta with bladder invasion. A plea for multidisciplinary approach.

Placenta previa percreta with the urinary bladder invasion is a rare but potentially lethal condition. It has an increasing clinical significance due to its association with previous cesarean sections and uterine curettage. Herein, we report on a patient with placenta percreta and bladder invasion, who presented with hematuria and in whom delivery was delayed to almost full term highlighting the potential catastrophic results and the need for a multidisciplinary approach with the need to involve surgeons who are familiar with vascular and urologic surgery. We also present an elegant MRI of placenta percreta invading the urinary bladder, which shows that MRI is potentially an excellent diagnostic modality in this difficult condition.

Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients.

We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion. Kaplan-Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation.