Synthesis and characterization of sulfur-containing hybrid materials based on sodium silicate.

An original method for the one-stage synthesis of sulfur-containing silica of SBA-15 type is developed and described. Instead of tetraethylorthosilicate (TEOS) typically used as a source of silica, the inexpensive sodium metasilicate has been applied in our method. The mesoporous silica material was first functionalized with thiol groups then oxidized by concentrated nitric acid to produce sulfonic groups. The samples obtained possess developed specific surface area (S sp = 320-675 m2 g-1) and porous structure with an effective pore diameter of 3.5-5.7 nm. The orderliness of the structure and presence of surface sulfur-containing acidic groups of various natures in the synthesized materials were determined using XRD, TEM, N2 adsorption, conductivity and potentiometric titration methods. Based on the results of the measurements of the zeta potential vs. pH and electrolyte concentration, conclusions about the electro-surface properties and aggregation stability of sample dispersion have been drawn. The obtained samples are environmentally-friendly and could be used in green chemistry.

Flocculation of Bacillus thuringiensis var. israelensis suspension and its efficacy against mosquito larvae.

Bacillus thuringiensis ssp. israelensis (Bti) is increasingly used as an ecologically friendly anti-mosquito agent. The bacterium cells undergo fermentation in dilute suspensions; before practical use, therefore it is necessary to concentrate the suspensions. Aggregation by polymers is a powerful tool with which to regulate the stability of suspensions. Typically, polymers at low concentrations destabilize and at high concentrations stabilize colloidal systems. Bti suspensions can be flocculated efficiently by either cationic or anionic polyelectrolytes. Cationic polyelectolytes were found to be the most efficient flocculants for bacterial suspensions. It was shown that the degree of toxicity of the flocculated Bti suspensions for biting mosquito larvae was in the same range than in non-flocculated suspension.

Pregnancy outcome among working women.

The influence of occupational factors on the outcome of pregnancy was investigated in a prospective study of 3901 women who worked during their pregnancy and received prenatal care in Orebro County from October 1980 to June 1983. Data on occupational factors, social circumstances, and life-style factors were obtained from questionnaires. There were no significant differences in the incidence of adverse pregnancy outcome (spontaneous abortion, perinatal death, birth defects, or low birthweight) between the nine occupational categories used when nonoccupational factors were accounted for. No increased risk was found for exposure to organic solvents, but the adjusted risk ratio of adverse outcome was 1.28 (95% CI 0.91-1.80) for "other chemical exposures." The work conditions in this county have been generally favorable in recent years, and the results therefore cannot be generalized to conditions with higher exposures. Methodological problems such as misclassification of exposure and the possible bias resulting from different rates of legal abortions among occupational groups are discussed.

Application of a primate model for tardive dyskinesia.

Persistent signs of oral dyskinesia (tongue protrusion and facial grimacing) had developed as a result of earlier chronic treatment with neuroleptics in a Cebus apella monkey. When this animal was given single doses of any classical neuroleptic, a transient deterioration of dyskinesia occurred, preceded by a temporary abolishment of dyskinesia sometimes with an attack of acute dystonia. Fluphenazine (5-25 micrograms/kg) causes dose-related deteriorations of dyskinesia. Six different drugs were tested on this monkey for their capacity to elicit aggravation of dyskinetic signs: three antihistamines (brompheniramine, promethazine, diphenhydramine) and three dopamine D2 receptor antagonists (sulpiride, tiapride, metoclopramide). High doses of promethazine and diphenhydramine (5 mg/kg) induced a temporary alleviation of dyskinesia, possibly through sedation. All three D2 receptor antagonists precipitated signs of acute dystonia at some dose levels, but out of the test drugs only metoclopramide caused deterioration of dyskinetic symptoms. According to the present results only metoclopramide stands out as a drug with an inherent propensity to cause tardive dyskinesia.

Development of acute dystonia and tardive dyskinesia in cebus monkeys.

In 4 out of 11 cebus apella monkeys given haloperidol (0.05 - 1.0 mg/kg/d) orally for up to 35 months signs of tardive dyskinesia (TD) hav developed: 1) One monkey developed barely noticeable TD after 4 months, but showed marked and increasing symtpoms of both generalized choreic and buccolingual TD after 8 months. This animal died 3 months after discontinuation of haloperidol. At that time the signs of TD were still prominent. 2) In one monkey bucco-lingual TD appeared after 3 months and was still reversible on discontinuation of haloperidol at 5 months. After a further 12 months of haloperidol, the TD signs proved to be long lasting, possibly irreversible, in this animal. 3) A third monkey showed slight and transient signs of TD at 14 months, but following a further 20 months af haloperidol administration a choreiform syndrome became porminent after drug withdrawal. 4) After 34 months a similar syndrome of choreic movements has been noticed in another animal, increasing after withdrawal of haloperidol. The other 7 monkeys have received haloperidol for 3 - 15 months, without developing any signs of TD. Attacks of acute dystonia have been noticed in all animals, sometimes necessitating anticholinergic medication or decreases in the daily haloperidol dose.

Pharmacological modification of experimental tardive dyskinesia.

Cebus apella monkeys subjected to chronic haloperidol administration develop neurologic disturbances very similar to neuroleptic-induced acute dystonia human beings. After varying lengths of time, certain monkeys develop a prolonged dyskinetic syndrome resembling tardive dyskinesia (TD), as seen clinically. Two monkeys with signs of TD were given single intramuscular injections of various compounds with known effects on the catecholaminergic, cholinergic, serotoninergic and GABA-ergic neurotransmittor systems, and their effect on the TD signs were rated. Dopamine receptor blockers as well as cholinergics had an ameliorating effect on the symptoms. Some compounds known to activate the GABA system, including some benzodiazepines and the GABA-transaminase inhibitor amino-oxyacetic acid, also reduced the symptoms, as did the serotonin precursor L-5HTP. Results with serotonin antagonists were equivocal. It is concluded that dopamine receptor blockade, as well as increased activity within the GABA-ergic or cholinergic systems cause alleviation of TD. The findings are in agreement with earlier reports in man and thus seem to validate this primate model.

A monitoring test for the liability of neuroleptic drugs to induce tardive dyskinesia.

Two Cebus apella monkeys with haloperidol-induced tardive dyskinesia have been studied. Substitution of chlorpromazine, thioridazine, clozapine, melperone, or fluphenazine for the daily haloperidol administration temporarily reduced the signs of tardive dyskinesia. In a monkey with low-grade symptoms, persisting for more than 100 days after withdrawal of haloperidol, neuroleptic drugs induced a typical sequence of events: first the dyskinetic movements were abolished, but 1--3 days after administration of a single dose of a neuroleptic drug there was a rebound worsening of symptoms. It was noticed that this aggravation of symptoms corresponded in magnitude and duration to the approximate liability of each compound to induce tardive dyskinesia in man. It is therefore suggested that this animal model could be used to monitor neurological side effects in neuroleptic drugs.

Clinical experience of naproxen in the treatment of primary dysmenorrhea.

The effect of naproxen, Naprosyn, Syntex, in treatment of primary dysmenorrhea was studied in a double-blind, randomized, placebo controlled multicenter study. Nintyseven women, aged between 18--40 years, with severe dysmenorrhea, were treated with either naproxen, 48 women, or placebo, 49 women, for two consecutive menstrual cycles. No oral contraceptive was used. The patients were allowed to take supplementary analgesics 4--6 hours after the study drug was taken if adequate relief was not achieved. The recommended dose of naproxen was 1--2 tablets, 250 mg, as needed, with a maximum of 5 tablets daily. Medication was started at first sign of menstrual distress. Improvement was achieved in 70 per cent of the women in the naproxen group (good to excellent relief) but only in 30 per cent in the placebo group. This difference is statistically significant (p less than 0.001). There was much more supplementary medication used in the placebo group compared to the naproxen treated patients (p less than 0.001). Fewer patients had to stay in bed, or stay at home from work or school, in the naproxen group compared to the placebo group. Few side-effects were reported and most of them belonged to the dysmenorrhea symptomatology. No side-effects could be rement according to the patients' own judgement.

Haloperidol-induced tardive dyskinesia in monkeys.

In three cebus monkeys the chronic daily administration of haloperidol (0.5 mg/kg/day orally) created sedation and parkinsonism during the first 5-7 weeks. Later the animals developed signs reminiscent of acute dystonia, as seen in the clinic during treatment with neuroleptics. These signs were dose-dependent and in extreme cases included widespread tonic and clonic seizures. After 3 and 12 months, respectively, two of the cebus monkeys developed buccolingual signs (grimacing and tongue protrusion), similar to tardive dyskinesia in the clinic. The tardive dyskinesia symptoms were reduced in a dose-dependent manner after each haloperidol administration, being most pronounced in the morning before haloperidol was given. Biperiden reduced acute dystonia but reinstated signs of tardive dyskinesia, which had been abolished by haloperidol. It is suggested that cebus monkeys may provide a useful animal model for the study of neurologic long-term complications from neuroleptic drugs.