Cyclization and unsaturation rather than isomerisation of side chains govern the selective antibacterial activity of cationic-amphiphilic polymers.

Membrane-active agents represent a promising alternative to overcome antibiotic resistance. Here, we report cationic-amphiphilic polymers with variations in the side chain architecture such as cyclization, isomerization and unsaturation that resulted in potent antibacterial activity and low mammalian cell toxicity with a membrane-active mode of action.

Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman.

Epilepsy in menopausal women presents several challenges in the treatment including an increased risk of seizures due to hormone replacement therapy. We investigated the hypothesis if raloxifene, a selective oestrogen receptor modulator, could be employed to prevent behavioural seizures and morphological alterations in a mouse model mimicking epilepsy in postmenopausal women. Female mice were made ovotoxic by treatment with 4-vinylcyclohexene diepoxide (VCD) to mimic a postmenopausal state. They were then subjected to kainic acid (KA)-induced seizures and neurotoxicity, as assessed by microscopic examination of hippocampus, relevant to human temporal lobe epilepsy. VCD administration (for 15days followed by a drug-free period of 30days) induced ovotoxicity in mice as evidenced by reduced number of primary ovarian follicles. This was accompanied by a 62.4% reduction in serum oestradiol levels. The bone mineral density of ovotoxic mice, however, remained unaffected. Raloxifene (8mg/kg) reduced the seizure severity score in both normal and ovotoxic mice and protected against degeneration induced by KA in the CA3, CA1 sub-fields and hilus of the DG. Hippocampal TGF-ß3 levels were not affected by any of the treatments. We show the potential protective role of raloxifene in preventing seizures and neuronal damage in a mouse model mimicking epilepsy in postmenopausal women which was found unrelated to hippocampal TGF-ß3. Raloxifene might represent a novel therapeutic option for postmenopausal temporal lobe epileptic woman.

Histamine H3 receptor antagonists in relation to epilepsy and neurodegeneration: a systemic consideration of recent progress and perspectives.

The central histaminergic actions are mediated by H(1) , H(2) , H(3) and H(4) receptors. The histamine H(3) receptor regulates the release of histamine and a number of other neurotransmitters and thereby plays a role in cognitive and homeostatic processes. Elevated histamine levels suppress seizure activities and appear to confer neuroprotection. The H(3) receptors have a number of enigmatic features like constitutive activity, interspecies variation, distinct ligand binding affinities and differential distribution of prototypic splice variants in the CNS. Furthermore, this Gi/Go-protein-coupled receptor modulates several intracellular signalling pathways whose involvement in epilepsy and neurotoxicity are yet to be ascertained and hence represent an attractive target in the search for new anti-epileptogenic drugs. So far, H(3) receptor antagonists/inverse agonists have garnered a great deal of interest in view of their promising therapeutic properties in various CNS disorders including epilepsy and related neurotoxicity. However, a number of experiments have yielded opposing effects. This article reviews recent works that have provided evidence for diverse mechanisms of antiepileptic and neuroprotective effects that were observed in various experimental models both in vitro and in vivo. The likely reasons for the apparent disparities arising from the literature are also discussed with the aim of establishing a more reliable basis for the future use of H(3) receptor antagonists, thus improving their utility in epilepsy and associated neurotoxicity.

Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs.

Voltage-gated sodium channel blockers like phenytoin and carbamazepine have long been used in the treatment of epilepsy. Brain sodium channels continue to be an important target of many newer second-generation (fosphenytoin, oxcarbazepine, lamotrigine, felbamate, topiramate, zonisamide) and third-generation (eslicarbazepine, brivaracetam, carisbamate, fluorofelbamate, elpetrigine, lacosamide, rufinamide, safinamide, vinpocetine) antiepileptic drugs (AEDs). Some of the newer drugs show either state-dependent antiepileptic action or sodium channel subtype selectivity, although most agents do not differentiate between these channel subtypes. The present review highlights the preclinical and clinical efficacy, pharmacokinetics, drug interactions and adverse event profiles. It also addresses AED selection of sodium channel blockers that constitutes the third generation of AEDs.

The chronic toxicity of inorganic mercury in goats: clinical signs, toxicopathological changes and residual concentrations.

Chronic mercury toxicity was induced in goats by administering mercuric chloride at 100 micrograms/ml in deionized drinking water offered ad libitum for 90 days. Toxic signs of gastrointestinal disturbances and renal dysfunction developed from 43 days onwards without any mortality. The toxicity also induced nephrosis and tubular nephritis; centrilobular necrosis of liver; mild to moderate necrosis in spleen, intestine and lymph node; Zenker's degeneration of cardiac muscles; exudative pneumonia; and pial congestion, oedema and vacuolation in the brain. In addition, hyperaemia, oedema and tissue haemorrhages were evident in most of the organs. The kidneys contained the largest residues of mercury, followed by liver, spleen, intestine, lymph node, skeletal muscles, lungs, heart, brain and the omental fat. The intensity of the cytotoxic changes in the various organs was proportional to the amount of mercury accumulated.

Synovial fluid changes in mycoplasma induced septicaemic polyarthritis of goat kids.

Synovial fluid samples of goat kids inoculated (ip) with 5 ml of 48 hr log phase culture of Mycoplasma mycoides sub sp. mycoides (large colony type) containing 10(7) cfu/ml were analysed for physical, cytological and biochemical properties. The synovial effusions were exudative in nature with increased volume. Gross appearances were serofibrinous, haemorrhagic and turbid containing flocculent materials with immediate clot formation. Mucinous precipitate quality was very poor having friable precipitates with cloudy supernatant. There were high total leucocytic and erythrocytic counts with significant high numbers of both neutrophils and lymphocytes. Synovial fluid sugar contents were significantly reduced, whereas total protein contents were significantly increased with concomitant reduction in albumin:globulin ratio. The alkaline phosphatase and transaminase values were also markedly increased in the synovial fluids of mycoplasma induced polyarthritic goat kids. The results may provide a clinical guideline for diagnosis, chemotherapy and prognosis of different joint diseases in domesticated animals.

Acquired immunity to Eimeria tenella in lasalocid-treated chickens.

The effect of restricted medication with lasalocid sodium on the development of acquired immunity against Eimeria tenella was evaluated. The medication was allowed for all or part of 6-day test period (one day before until 4 days after infection). The parameters used for such evaluations were lesion score, caecal, bursal and splenic weights. The optimum treatment time for the drug was clearly indicated by lesion score which was very low when the medication was initiated 1 day before until 1 day after inoculation, but only partly effective if given on Day 2 post-inoculation. The challenge with higher doses on 14th day of immunizing infection revealed a reverse picture where the higher lesions were recorded by the groups where medication was started earlier than the delayed treatment groups. This indicates partial interference with the development of immunity in the earlier treatment groups. Birds treated on Day 4 p.i. were not significantly different (P less than 0.05) from the infected unmedicated control group, suggesting no interference in acquired immunity. A correlation was noticed between day of treatment, the lesion score and weight gain of the caecum as well as the spleen. After both immunizing and challenge infections, the bursa did not show any significant variation in weight, whereas the weight of the spleen did vary. The infected unmedicated group and the delayed-treatment groups had a comparatively higher splenic weight than the uninfected unmedicated group of birds.(ABSTRACT TRUNCATED AT 250 WORDS)