Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats.

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na2SeO3) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na2SeO3 (2 mg/kg), and AMPH + PDG + Na2SeO3. The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na2SeO3 significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na2SeO3 improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na2SeO3 displayed markedly lower IL-1ß and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na2SeO3. The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na2SeO3 may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery.

Selenium Nanoparticles with Prodigiosin Rescue Hippocampal Damage Associated with Epileptic Seizures Induced by Pentylenetetrazole in Rats.

BACKGROUND: Prodigiosin (PDG) is a red pigment synthesized by bacterial species with important pharmaceutical and biological activities. Here, we investigated the neuroprotective and anticonvulsant activities of green biosynthesized selenium formulations with PDG (SeNPs-PDG) versus pentylenetetrazole (PTZ)-induced epileptic seizures. METHODS: Rats were assigned into six experimental groups: control; PTZ (60 mg/kg, epileptic model); sodium valproate (200 mg/kg) + PTZ; PDG (300 mg/kg) + PTZ; sodium selenite (0.5 mg/kg) + PTZ; and SeNPs-PDG (0.5 mg/kg) + PTZ. The treatment duration is extended to 28 days. RESULTS: SeNPs-PDG pre-treatment delayed seizures onset and reduced duration upon PTZ injection. Additionally, SeNPs-PDG enhanced the antioxidant capacity of hippocampal tissue by activating the expression of nuclear factor erythroid 2-related factor 2 and innate antioxidants (glutathione and glutathione derivatives, in addition to superoxide dismutase and catalase) and decreasing the levels of pro-oxidants (lipoperoxidation products and nitric oxide). SeNPs-PDG administration inhibited inflammatory reactions associated with epileptic seizure development by suppressing the production and activity of glial fibrillary acidic protein and pro-inflammatory mediators, including interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, SeNPs-PDG protected against hippocampal cell loss following PTZ injection by decreasing the levels of cytosolic cytochrome c, Bax, and caspase-3 and enhancing the expression of anti-apoptotic Bcl-2. Interestingly, SeNPs-PDG restored the PTZ-induced imbalance between excitatory and inhibitory amino acids and improved monoaminergic and cholinergic transmission. CONCLUSIONS: These promising antioxidative, anti-inflammatory, anti-apoptotic, and neuromodulatory activities indicate that SeNPs-PDG might serve as a naturally derived anticonvulsant agent.

Trend in the annual risk of tuberculous infection in Egypt, 1950-1996.

OBJECTIVE: To determine the trend in the risk of tuberculous infection in non-BCG vaccinated children in Egypt in the period 1950-1996. METHODS: In 1949-1952, a tuberculin survey was carried out in Egypt by the World Health Organization (WHO) covering 103 districts. In 1995-1997 a tuberculin survey was carried in 73 620 primary school children in grade one in the same districts, using international guidelines. The trend in tuberculous infection was determined by comparing the prevalence of Mantoux reactions of > or =6 mm in the two surveys in subjects without apparent BCG scar aged 6-7 years. For an estimate of current risk of infection the 17 mm cut-off point (number with 17 mm plus twice the number with greater than 17 mm) was used. RESULTS: In 1995-1997, 76% of children had a BCG scar. Infection prevalence estimates in 14 766 non-BCG-vaccinated children with a mean age of 6.7 years were 11.9%, 4.1%, and 2.1% for the cut-off points 6 mm, 10 mm, and 17 mm, respectively. Decline in the risk of infection was estimated to be in the order of 50% over 45 years, or 1.5% per year. The geometric mean annual risk of infection in the 6.7 years before the survey was estimated at 0.32% (95% confidence interval 0.27-0.40%). For Egypt, the incidence of smear-positive tuberculosis was estimated at 16 per 100000 population, giving a case detection rate of 85% (range 56-100%). CONCLUSION: This survey has shown that the size of the tuberculosis problem in Egypt is considerably smaller now than it was 45 years ago.

Systemic lupus erythematosus in Kuwait--hospital based study.

The present study describes the clinical characteristics of patients with systemic lupus erythematosus (SLE), from the rheumatology service of the two main teaching hospitals in Kuwait. It was a retrospective-cum-prospective clinical study of 108 SLE patients. There were 98 females and 10 males, with a median age of 31.5y. Kuwaitis constituted 69%, while 31% were expatriates. The mean disease duration was 62 months. The main clinical features were: musculoskeletal involvement (87%), photosensitivity (48%), malar rash (43%), discoid lesions (10%), oral ulcers (33%), vasculitic skin lesions (10%), haematological features (53%), constitutional symptoms (51.4%), neuropsychiatric manifestations (23%), renal involvement (37%), serositis (29%), clinical manifestations of antiphospholipid syndrome (21%), cardiac involvement (10%) and pulmonary manifestations (19%). In conclusion, the clinical features of SLE in Kuwait were similar to most major studies from developed countries. Main differences included prominent haematological and mucocutaneous manifestations and possibly a low prevalence of anti-Sm antibodies. Whether these differences are due to the environment or genetic factors, remains to be studied.

Hughes syndrome: a common problem in Kuwait hospitals.

The objective was to study antiphospholipid antibody syndrome (APS or Hughes syndrome) in two major teaching hospitals in Kuwait. patients with suspected Hughes syndrome were investigated with tests for anticardiolipin antibodies (aCL) and lupus anticoagulants (LAC) over 1 yr. Diagnosis was considered confirmed if significant levels of either or both antibodies with no obvious cause (primary), or with systemic lupus erythematosus (SLE) or SLE-like illness (including SLE serology) (secondary) were present. Twelve (37.5%; seven females, 58%) primary and 20 (62.5%; 18 females, 90%) secondary Hughes syndrome patients were seen during this period. patients were Kuwaiti, Middle-Eastern and North-African Arabs (29). Filipinos (2) and White (1). None were from the Indian subcontinent. The main presentation was thrombosis in 75% (arterial in 25% and venous in 50%), and recurrent abortions in 50% of married women. Haematological and dermatological manifestations were limited entirely to the secondary variety, seen in 25% and 19%, respectively. Clinical manifestations were severe, leading to death in one, intensive-care management in 31% and with partial or complete warfarin resistance or brittleness in 25%. Neurological/eye and cardiac manifestations were not seen, as these patients may be attending separate speciality hospitals for these diseases in Kuwait. The approximate prevalence of this syndrome was 2.66/1000 admissions in medical wards. Projected to the total referral areas of the two hospitals, an approximate figure of 52 patients/million population/year was obtained. Hughes syndrome was a common problem among Arabs, Filipinos and possibly Whites in Kuwait. Its manifestations were severe, often requiring intensive-care management, and in one case it was fatal. Patients from the Indian subcontinent were conspicuous by their absence, despite the fact that they were well represented in all other rheumatic disease groups. Ethnic and/or geographical factors could be important in this syndrome. To the best of our knowledge, this is the first report of Hughes syndrome from the Middle East.

Quantitative evaluation of ECG components of workers exposed to carbon disulfide.

The components of electrocardiograms (ECG) of 253 workers exposed to carbon disulfide (CDS) and those of 99 controls were quantitatively measured and evaluated. ECG of the exposed workers showed a statistically significant higher prevalence of ECG pathological changes, higher P amplitude and Macruz index, longer P duration, longer both crude and corrected Q-T intervals and R-R intervals and shorter P-R segments and QRS intervals than that of the controls. On the other hand, P-R intervals and heart rates of the two groups were not significantly different. Among both the the exposed and control groups, values of P duration were significantly negatively correlated with that of P-R segment: r = -0.216 and -0.132, respectively, p greater than 0.05. Values of the ECG components were not related to duration of exposure to CDS. Moreover, no significant difference was observed between duration of exposure of the exposed workers with and of those without pathological ECG changes. The method used in our study may be useful in evaluating the ECG of exposed workers before the appearance of the known pathological abnormalities.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 6: Effect of drug.

The effect of addition of ascorbic acid, which is a drug known to be difficult to compress directly, on the self-binding efficiency of tragacanth, Carbowax 4000, Plasdone, and mannitol were investigated. The flow properties of ascorbic acid of different particle sizes were determined since they would affect the flowability of the binders investigated and would help to determine the optimum particle size of the drug required for maximum binding efficiency.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 7: Formulation and evaluation of ascorbic acid and phenobarbitone tablets.

Directly compressible powder blends containing either ascorbic acid or phenobarbitone, and utilizing tragacanth, Carbowax 4000, Plasdone, and mannitol as dry binders, were formulated. The flowability of the powder mixes prior to compression was determined. Furthermore, the tablets prepared according to the suggested formulae were tested for hardness, friability, uniformity of weight, distribution of active ingredient, disintegration, and dissolution. The effect of aging on the qualities of the tablets was also studied.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 5: Effects of lubricants and flow conditions.

The effect of talc, magnesium stearate, stearic acid, and Acrawax C, which are commonly used as lubricants, on the dry-binding efficiency of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone, and mannitol were investigated. The effect of Aerosil which is sometimes utilized as a flow conditioner for directly compressible powder blends was also studied. The type and concentration of lubricant or flow conditioner appeared to influence the binding efficiency of the binders investigated to various degrees. The results showed that the bonding characteristics of all the binders tested except mannitol were reduced by the addition of the lubricants and the flow conditioner.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 3: Effect of diluents.

The effects of lactose and dibasic calcium phosphate as diluents on the dry-binding qualities of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone and mannitol were investigated. The type, concentration and particle size of the diluent appeared to influence the flowability and the binding properties of the binders investigated.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 4: Effect of disintegrants.

The effects of starch and Veegum as disintegrants on the dry-binding qualities of tragacanth, polyethylene glycol 4000, polyvinylpyrrolidone and mannitol were investigated. The type of diluent and its concentration in the powder blends appeared to influence the binding efficiency of the binders investigated.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 2: Comparative self-binding properties.

Comparative self-binding qualities of four substances studied as potential dry binders for direct compression applications in tablet making were investigated. The effect of particle size of these materials on hardness, friability and hardness-friability ratio of disks made with mere binders was studied. The results showed that for comparable particle sizes, values of hardness-friability ratio of the various disks were in the following descending order: Plasdone, tragacanth, Carbowax 4000 and then mannitol.

Investigation of some materials as dry binders for direct compression in tablet manufacture. Part 1: flow properties and water sorption.

Four substances were evaluated for their potential usefulness as dry binders for direct compression techniques in tablet making. The flow properties of these substances including angle of repose, timed delivery through an orifice and compressibility were determined. The effect of particle size of the binder on its flow properties was investigated. Comparative rates of water sorption demonstrated by the various substances evaluated as dry binders were also determined.