Responses of microglia in vitro to the gram-positive bacterial component, lipoteichoic acid

An increase in incidence and severity of gram-positive infections has emerged in the past decade. In this regard, attention has been focused recently on immune responses of microglial cells in the central nervous system to gram-positive bacteria. The underlying immunological and cellular events in microglial activation induced by specific bacterial toxin of gram-positive bacteria, however, have not yet been clarified fully. This study reports that a simple cell wall product, lipoteichoic acid (LTA), derived from gram-positive bacteria (Staphylococcus aureus) could trigger microglial activation in vitro. Microglia challenged with LTA showed intense ruffling of plasma membrane in the form of lamellipodia or rounded up forming cell aggregates. MTT assay and Western blot analysis with anti-proliferating cell nuclear antigen antibody showed a significant microglial proliferation that may be induced at the later phases of LTA treatment with low doses but at the early period with a high dose. Concentrated LTA also caused apoptotic death of cultured microglia showing fragmented nuclei and increased expression of annexin V or caspase 3. In response to LTA, isolated microglia increased the expression of inducible nitric oxide synthase and major histocompatibility complex class II antigen. Microglial LTA receptors such as CD14 molecule, complement receptor type 3, and macrophage scavenger receptor were upregulated concurrently. In conclusion, staphylococcal LTA can exert an immunomodulatory effect on microglial morphology, cell cycle, and immunomolecules, including its receptors.     

Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study

CONTEXT: Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia. OBJECTIVE: To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient units of 2 major medical centers in Taiwan.Patients Sixty-five schizophrenic inpatients with acute exacerbation. INTERVENTIONS: Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy. MAIN OUTCOME MEASURES: Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores. RESULTS: The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P< or =.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P< or =.04 for all). D-serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains. CONCLUSIONS: This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.     

Rare extra-articular manifestation of rheumatoid arthritis: scleromalacia perforans

Rheumatoid arthritis is a systemic disease with manifestations in many organs. In most cases, involvement of the locomotor system dominates the clinical picture. However, extra-articular manifestations can be detected in almost any organ system with varied incidence in different series. Ophthalmic presentations include Sjogren's syndrome, episcleritis, and scleritis. The most severe form of scleritis, scleromalacia perforans, is a very rare ophthalmic manifestation. We present the case of a 60-year-old man who had had rheumatoid arthritis for more than 10 years. He had scleromalacia perforans but no other extra-articular manifestations.     

Hypophosphatasia in Taiwan: report of two cases

Hypophosphatasia is a rare inherited metabolic disease characterized by rickets with reduced plasma and tissue alkaline phosphatase activity. It may be present in infancy, childhood, or adulthood. Various clinical manifestations reflect different forms of alkaline phosphatase gene expression. In this report, we present two cases of hypophosphatasia, one of the infantile and the other of the adult form. The infantile case presented with failure to thrive, hypotonia, and radiologic rickets at 4 months old. The adult case had repeated fractures and marked loss of bone density demonstrated by radiographs. Both cases showed extremely low levels of alkaline phosphatase. To the best of our knowledge, they are the first reported patients with hypophosphatasia from the Taiwanese population.     

The serum uric acid and related cardiovascular risk factors in south Taiwan

Hyperuricemia has been shown to be related to cardiovascular morbidity and mortality. Uric acid is a metabolic product synthesized from nucleic acids, amino acids and the Krebs cycle, reflecting a multiple metabolic associations in humans. The relation between uric acid and various cardiovascular metabolic parameters in Asians has rarely been reported on. In this study, we report the relationship between uric acid and various cardiovascular risk factors in 1,027 healthy Taiwanese adults living in Alien, an agricultural town in subtropical South Taiwan. Serum uric acid levels increased in proportion to age in women, but not in men. There were age and gender-specific correlations between uric acid and various cardiovascular metabolic parameters. Triglycerides and creatinine levels were two independent factors predicting serum uric acid levels in men, while only creatinine predicted uric acid levels in women of all age groups. Processes that influence the metabolism of uric acid and its association with other metabolic parameters differs by gender and age.     

Abbreviated duration of superheat-and-flush and disinfection of taps for Legionella disinfection: lessons learned from failure

One medical center in southern Taiwan faced an outbreak of nosocomial Legionnaires' disease; a total of 81 suspected cases were detected during an 8-month period. Baseline environmental surveillance showed that 80% of the distal sites in intensive care units (ICUs) were positive for Legionella pneumophila. Superheat-and-flush was selected for hospital water supply disinfection because it required no special equipment, and it can be initiated expeditiously. We conducted 2 episodes of superheat-and-flush based on the published recommendations from the Department of Health, Taiwan; US Centers for Disease Control and Prevention; and American Society of Heating, Refrigerating, and Air-Conditioning Engineers. Both flushes failed to control colonization of Legionella in the hospital water supply. The rate of distal sites positive for Legionella in wards and ICUs was 14% and 66%, respectively, 10 days after the second flush. The effect of replacement of faucets and showerheads in ICUs appeared to be insignificant in colonization of Legionella. The application of superheat-and-flush for flush duration of 5 minutes was ineffective. Superheat-and-flush may not be economic for a large medical center because it could be costly and labor intensive.     

The effect of combination therapy with propylthiouracil and cholestyramine in the treatment of Graves' hyperthyroidism

OBJECTIVE: The study aims to evaluate the efficacy of combination therapy with propylthiouracil (PTU) and cholestyramine in the treatment of Graves' hyperthyroidism. BACKGROUND: Thyroxine (T4) is metabolized mainly in the liver by conjugation to glucuronides and sulphates that enter the enterohepatic circulation. Thyrotoxic patients have an abnormal increase in thyroid hormone in their enterohepatic circulation. Previous studies on combination therapy with methimazole and cholestyramine for Graves' hyperthyroidism have shown it to be an effective adjunctive treatment. In this study, we examined the efficacy of combination therapy with PTU and cholestyramine in the treatment of Graves' hyperthyroidism. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups: group I (n = 15) received PTU 100 mg twice a day, propranolol 40 mg twice a day and cholestyramine 4 g twice a day for 4 weeks; group II (n = 15) received PTU 100 mg twice a day and propranolol 40 mg twice a day for 4 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), free thyroxine (FT4) and TRAb levels at baseline, and at the end of 2 and 4 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. At the end of 2 and 4 weeks of the study period, serum TT3 and FT4 levels of group I were significantly lower than those of group II. No significant differences in the TRAb level were found between the two groups. CONCLUSION: Cholestyramine contributed to a more rapid and complete decline in thyroid hormone levels in patients with Graves' hyperthyroidism. It was thus proved to be an effective and well-tolerated adjunctive therapy.