Journal of International Medical Research

We examined the antibacterial susceptibility of Staphylococcus aureus isolated from several types of skin infections, which were classified into four groups: (i) impetigo, (ii) folliculitis, (iii) atopic dermatitis and eczema and (iv) ulcers and decubitus. The 50% minimal inhibitory concentration (MIC₅₀) of the antibacterial agents was 3.13 μg/ml or lower, except that of gentamicin with isolates from the impetigo groups (25 μg/ml). The MIC₉₀ of gentamicin was 50 μg/ml or more for isolates from all four groups. The isolates from the ulcers and decubitus group showed multiple resistance against antibacterial agents. The frequency of methicillin-resistant S. aureus was low, but was highest, at 25%, in the isolates from the ulcers and decubitus group. Few isolates from the atopic dermatitis and eczema group were resistant, and there was little difference in antibacterial resistance between isolates from atopic dermatitis and eczema.

The antioxidant potential of Ginkgo biloba extract (EGb 761) on healthy human erythrocyte membranes was investigated. Lipoperoxidation was induced in erythrocyte suspensions using hydrogen peroxide, in the presence of EGb 761 at 37 °C; malondialdehyde production was determined as the indicator of lipoperoxidation during the incubation period. The results for EGb 761 at concentrations of 0, 25, 50, 125, 250 and 500 μg/ml suggest that the antioxidant potential of EGb 761 in erythrocyte membranes increases with dose. Similarly, using different incubation periods (0, 15, 30, 45 or 60 min) indicated that the antioxidant effect of EGb 761 increased by the incubation time.

From this presentation it becomes apparent that preclinical investigation of new drugs is a multi-disciplinary endeavour. The need for close team work between the various scientists is necessary to meet this complex research challenge successfully.

With the development of an ever-increasing number of potent drugs, it is mandatory that the physician responsible for monitoring new drug trials broaden his understanding of preclinical investigations. In doing so, he will soon learn the need for consistent interplay between the preclinical scientist and clinician.

Antipsychotic drugs are widely used to treat abnormal behaviour particularly that related to the functional psychoses such as schizophrenia. This review discusses the pharmacokinetics and pharmacology of antipsychotic drugs like chlorpromazine. Clinical use comprises the induction of tranquillization in disturbed psychiatric patients, the treatment of acute and chronic schizophrenic symptoms, and the postponement of relapse in such patients. Unwanted effects are multifarious, involving many systems of the body. Extrapyramidal signs and symptoms are particularly noticeable, and the chronic type, tardive dyskinesia, is a major problem.

Thirty children over the age of one month were treated with amikacin (BBK8), a new aminoglycoside derived from kanamycin A, with three intramuscular dosage schedules. Each group consisted of ten patients. The first received 7.5 mg/kg/12 hours, the second 7.5 mg/kg/24 hours and the third, 3.75 mg/kg/12 hours. The infections and the bacteria were similar in all three groups: pyelonephritis, abscesses of soft tissues, infected wounds, septicaemia, superinfected empyema, gastro-enteritis, chronic otitis media; the bacteria were E. coli, Klebsiella, Pseudomonas and Salmonella. A were sensitive by the Kirby-Bauer method, although two were resistant by dilution in Petri dish. Of the thirty patients, twenty four (80%) were cured. The schedule of 3.75 mg/kg/12 hours was as effective as the schedule of7.5 mg/kg/12 hours for infections such as pyelonephritis, superficial abcesses, contaminated wounds, gastro-enteritis and sepsis. The cases with infections localized in rather unaccessible sites required double the dose and strict drainage and cleanliness. Plasma levels with the administration of 3.75 mg/kg fluctuated between 8.3 and 12.6 mcg/ml; with 7.5 mg/kg they fluctuated between 8.6 and 13.1. The minimum inhibitory level (MIL) for the majority of the bacteria was 1.25 mcg/ml. No toxic reactions were observed.

The anti-hypertensive effect of timolol maleate (MK-950) was evaluated in patients with mild or moderate hypertension, in a double-blind, randomized, placebo controlled clinical trial.

The study was divided into a baseline placebo period, that lasted 9 weeks, during which documentation was made of the patient's untreated diastolic blood pressure. A 9 week titration period followed the placebo period, at which time patients were randomly assigned to an MK-950 or matching placebo group; the titration period was devoted to finding out the optimal dose of MK-950 or its matching placebo. The titration period was followed by a 6 week maintenance period during which patients were maintained on their optimal MK-950 or placebo dose.

Timolol is an effective anti-hypertensive drug and significantly reduces diastolic blood pressure. Its effect becomes apparent at the first week of treatment, and reaches maximum effectiveness at 4 weeks of treatment. The diastolic blood pressure in the timolol group remained consistently below 90 mm Hg and at the end of the study, the average diastolic blood pressure was: 88·57 ± 8·6 mm Hg (p > 0·001 in comparison with placebo). The average daily dose of timolol maleate was 31·10 ± 1·80 mg.

MK-950 has a strong negative chronotropic effect, capable of reducing the resting heart rate by an average of 28·50 beats/min. No correlation could be established between heart rate and blood pressure lowering effect. Other than bradycardia, no important side-effects were observed.

Our previous work has shown that the addition of diphenhydramine hydrochloride to platelet-rich plasma is capable of causing disaggregation of platelet aggregates already induced by adenosine diphosphate as well as of inhibiting platelet aggregation when added prior to the aggregating agent. This led us to attempt to prevent arterial thrombosis in a canine experimental model. Ten dogs received an injection of diphenhydramine (approximately 3 mg/kg of body-weight) into the right common femoral artery 1 cm proximal to the proximal end of a 2 cm endarterectomy immediately after closure of the endarterectomy site and prior to performing an endarterectomy of the other common femoral and both common carotid arteries. The dogs which received diphenhydramine were compared with ten control dogs and found to have no protection against thrombosis at the sites of endarterectomy after 4 and 24 hours.

Cyclosporin A (CsA), a non-myelotoxic immunosuppressant, and its metabolites are widely distributed in the body. Highest concentrations of CsA have been detected in the pancreas, adipose tissue and liver, lowest concentrations in brain, muscle, blood and other body fluids. Metabolites are distributed differently to CsA. In addition to lipid partition, intracellular binding to cyclophilin, a peptidyl–prolyl cis–trans isomerase, appears to play a role in its tissue distribution. The temperature dependence of such binding in erythrocytes poses difficulty in serum or plasma measurements. Tissue specific processes may also influence action and toxicity of CsA and its metabolites; thus, a better understanding of the complex distribution pattern of CsA and its metabolites would be important for establishing improved strategies and selection of appropriate specific methodologies for drug monitoring.

Osteoarthritis (OA) is the most prevalent degenerative joint disease and is accompanied by pain and joint dysfunction. Its clinical treatment tends to be unsatisfactory. Novel targets in OA include genes that are involved in OA pathophysiology and have been discovered using gene network, epigenetic and microRNA (miRNA) approaches. miRNA has been implicated in important cellular processes such as lipid metabolism, apoptosis, differentiation and organ development. The importance of miRNA regulation in cellular function is becoming increasingly clear as new miRNA targets are revealed. The present review summarizes the current evidence of the important role played by miRNA in determining the complex gene expression patterns of OA chondrocytes and their role in the regulation of transcription, and possible demethylation mechanisms that might be applicable in OA. In summary, miRNA may have important diagnostic and therapeutic potential, and might provide a novel means of treating OA.

The original glucose-based formulation of Betaferon®/Betaseron® (interferon beta-1b) requires refrigerated storage. A refrigeration-free formulation of interferon beta-1b, based on mannitol, is stable at room temperature for up to 2 years, and offers a greater degree of flexibility for patients with multiple sclerosis (MS). We compared the safety and tolerability of the two formulations in a 24-week, randomized, double-blind, parallel group, Phase IV clinical study conducted in 303 patients with MS. Patients received the glucose formulation (IFNβ-1b-G) for 8 weeks, and were then randomized to receive either IFNβ-1b-G or the refrigeration-free formulation (IFNβ-1b-M) for a further 8 weeks. On completion of the double-blind phase, all patients received IFNβ-1b-M for an 8-week follow-up period. The primary outcome measure was the proportion of injection sites that developed reactions per patient during the double-blind period. In addition, a range of secondary outcomes relating to these reactions was also assessed. The difference in the proportion of injection-site reactions between the two groups was not statistically significant (59% IFNβ-1b-G versus 60% IFNβ-1b-M). There were no statistically significant differences observed between the two treatment groups in any of the secondary tolerability endpoints. The results from this study demonstrate that the tolerability and safety profiles of both formulations are extremely good, and that the refrigeration-free formulation of interferon beta-1b is comparable with that of the original glucose formulation.

Dietary fiber is widely recognized to have a beneficial role in overall health, but only at adequate levels (25 − 38 g/day for healthy adults). Wheat dextrin in particular is a soluble fiber that can easily be added to the diet and is widely used in the food industry. There is some debate about whether increased intake of soluble fibers leads to health benefits. This paper reviews the evidence regarding the physiological effects and potential health benefits of the addition of soluble dietary fibers, with specific reference to wheat dextrin, based on a search of PubMed. The evidence suggests that soluble fibers help to regulate the digestive system, may increase micronutrient absorption, stabilize blood glucose and lower serum lipids, may prevent several gastrointestinal disorders, and have an accepted role in the prevention of cardiovascular disease. It is concluded that supplementation with soluble fibers (e.g. wheat dextrin) may be useful in individuals at risk of a lower than recommended dietary fiber intake.

Cell wall-deficient bacteria (CWDB) are pleomorphic bacterial forms. These atypical organisms may occur naturally or they can be induced in the laboratory. Their presence has been known about for over a century, but a definite link to clinical disease outcomes has not been demonstrated. A number of case reports and laboratory studies suggest some disease associations, however. Considerable controversy surrounds the true relevance of CWDB to disease; there is a widespread belief that they may represent a response by the walled organism to adverse extracellular conditions like antibiotic pressure. This review looks at studies published between 1934 and 2003, which were identified by Dialog DataStar using the key words ‘cell wall deficient bacteria and clinical significance and infections’ and by further scanning the reference list at the end of the papers retrieved. We conclude that the evidence for the clinical significance of CWDB in disease is not compelling.

Osteosarcoma is a primary malignant bone tumour with high morbidity that occurs mainly in children and adolescents. While the molecular basis of osteosarcoma has received considerable attention, the cellular and molecular mechanisms underlying pre- and postoperative metastasis formation and the development of chemoresistance remain unclear. MicroRNAs (miRNAs), a class of 22-nucleotide noncoding RNAs, have emerged as critical components of gene-regulatory networks controlling numerous important pathophysiological processes, including the initiation and progression of cancers. Studies on miRNAs have opened new avenues for both the diagnosis and treatment of cancer. This review discusses the roles of miRNAs in osteosarcoma and their potential applications for the diagnosis, prognosis and treatment of this malignancy. As a rapidly evolving field of basic and biomedical science, miRNA research will have a revolutionary impact on the management of osteosarcoma.

There has been much media speculation (often sensationalist and conflicting) regarding the potential influence of micronutrients on cognitive function and performance. Our aim was to identify the micronutrients specifically implicated in cognitive function and to review the literature to identify original sources underlying the media coverage. Literature searches were carried out to identify recent clinical trials, reviews, editorials and meetings describing the biochemical and physiological role of individual micronutrients. No attempt was made to grade the evidence. The searches confirmed that the water-soluble vitamins (B group and C), together with the minerals, calcium, magnesium and zinc, are most relevant to cognitive performance. Clinical evidence revealed that marginal deficiencies of one or more of these micronutrients are not uncommon, even in the developed countries, and that such deficiencies may affect cognitive performance, especially in vulnerable groups such as the elderly and those individuals who are exposed to occupational pressures and a stressful lifestyle.

Anaemia often occurs in cancer patients and its origin is multifactorial, resulting from either bone marrow infiltration of cancer cells or cytotoxic effects produced by chemotherapy and radiotherapy. Anaemia impacts significantly on quality of life and appears markedly to limit disease control. Erythropoietin stimulates erythrocyte formation and the human recombinant form is useful in treating anaemia in cancer patients. Over the past decade erythropoietin has been associated with amelioration of anaemia and reduced need for blood transfusions. Nevertheless, several pre-clinical and clinical trials, employing relatively high doses of erythropoietin, have been halted recently following increased mortality and morbidity, primarily due to thrombotic events and possible tumour growth stimulation. It is, therefore, too early to know whether erythropoietin is useful in controlling morbidity and mortality in cancer-related anaemia. The risk–benefit of erythropoietic agents should be studied in carefully controlled trials. This review discusses prevalent issues and addresses key questions concerning the use of erythropoietic agents for the treatment of cancer-related anaemia.

Anti-epileptic drugs frequently interact due to pharmacokinetic features (induction or inhibition of metabolism, production of active metabolites, low therapeutic indices) and the need for prolonged treatment with possible addition of other drugs to treat concomitant diseases. The most important pharmacokinetic interactions are those that inhibit phenytoin, carbamazepine and phenobarbitone metabolism and thus increase their toxicity. Drugs inhibiting metabolism include antibiotic macrolides, chloramphenicol, isoniazide, some sulphonamides, propoxyphene, cimetidine, valproic acid and sulthiame. Anti-epileptic drugs can induce hepatic microsomal enzymes and, therefore, may increase metabolism of corticosteroids, oral contraceptives, oral anticoagulants, cardiovascular agents, antibiotics, chemotherapeutic agents, psychotropic drugs and non-opiate analgesics, thereby reducing their efficacy. Advantageous pharmacodynamic interactions include synergism of ethosuximide plus valproic acid and of carbamazepine plus valproic acid. A pharmacodynamic mechanism may be responsible for the reduced sensitivity of chronically treated epileptics to some neuromuscular blockers.

The authors conducted a clinical investigation on sixty-nine pregnant women, anaemic and non-anaemic, the purpose being to assess the effect of 50 days treatment with four different medicinal iron preparations, namely, ferrous sulphate, iron chondroitinsulfuric acid complex, and ferritin alone or associated with folinic acid and cobamamide, on various haematological parameters (Hb, RCC, Ht, CV, Iron, and Transferrin IBC).

The four products demonstrated a similar efficacy in maintaining anaemic conditions under control; moreover, the results confirmed our hypothesis of the absorption of iron ferritin. While three products were well tolerated, ferrous sulphate induced, in some cases, side-effects.