Reduction in the amplitude of shortening and Ca(2+) transient by phlorizin and quercetin-3-O-glucoside in ventricular myocytes from streptozotocin-induced diabetic rats.

Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca(2+), respectively. Blood glucose in STZ rats was 4-fold higher (469.64+/-22.23 mg/dl, n=14) than in Controls (104.06+/-3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76+/-2.91 %, n=20) and Control (83.72+/-2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12+/-2.28 %, n=20) and Control (76.69+/-1.92 %, n=30) myocytes. The amplitude of intracellular Ca(2+) was also reduced by PHLOR in STZ (82.37+/-3.16 %, n=16) and Control (73.94+/-5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62+/-5.83 %, n=18) and Control (78.32+/-3.54 %, n=41) myocytes. Myofilament sensitivity to Ca(2+) was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca(2+) in STZ or Control myocytes. Altered mechanisms of Ca(2+) transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats.

Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.

In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca(2+) transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca(2+) transients, myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+), and intracellular Ca(2+) current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440 ± 25 mg/dl, n = 21) compared to Controls (98 ± 2 mg/dl, n = 19). DAPA reduced the amplitude of shortening in Control (76.68 ± 2.28 %, n = 37) and STZ (76.58 ± 1.89 %, n = 42) ventricular myocytes, and reduced the amplitude of the Ca(2+) transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45 ± 5.35 %, n = 16) myocytes compared to Controls (92.01 ± 2.72 %, n = 17). Myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+) were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca(2+) current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca(2+) transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats.

Successful treatment of severe thrombocytopenia with romiplostim in a pregnant patient with systemic lupus erythematosus.

We present a case of a pregnant woman at 27 weeks of gestation with systemic lupus erythematosus who developed severe thrombocytopenia presenting with melena, epistaxis, gum bleeding and frank hematuria. She was resistant to most treatment modalities, including steroids, intravenous immunoglobulins (IVIG), rituximab, IV cyclophosphamide and eltrombopag. She responded to romiplostim with normalization of her platelet count, which enabled her to be delivered safely at 34 weeks of gestation.

Prostatic-specific antigen and idiopathic hirsutism in females.

Serum prostatic-specific antigens (PSA) were found recently to be present in several female tissues and fluids. High concentrations of PSA were found in hirsute women in comparison with nonhirsute, as was found in other studies. In our study we measured the level of PSA in 20 hirsute and 10 control subjects by using an IMx machine from Abbot Laboratories (Diagnostic division, Abbot Park, Illinois 60064, USA). The age, BMI, F-G score, duration and family history of hirsutism were recorded for both groups. The results were analyzed by using SPSS. We conclude that there is no significant association between the level of PSA and the presence of hirsutism. Usage of this test as a marker of idiopathic hirsutism needs further evaluation.

Rheumatoid arthritis and macrovascular disease.

OBJECTIVE: To measure the extent of subclinical atherosclerosis in patients with rheumatoid arthritis (RA) compared with controls, and to evaluate any potential vascular risk factors. METHODS: Forty RA patients were compared with an age- and sex-matched control group. Non-invasive vascular tests, i.e. carotid duplex scanning [measuring common carotid artery intima-media thickness (IMT)], ankle-brachial blood pressure index (ABPI) and QT dispersion on ECG (QTD), were performed. Traditional risk factors such as high blood pressure, blood sugar, lipids and steroid usage were assessed. RESULTS: The average IMT (S.E.) in RA patients was 0.73 (0.03) mm, compared with 0.62 (0.03) mm in the control group (P=0.01, Mann-Whitney). Ten out of 40 RA patients (25%) had an ABPI < 1.0 compared with 1/40 (2.5%) in the control group (P=0.007, Fisher's). QTD was higher in RA patients; mean (S.E.) 55 (2.70) ms compared with 40 (2.50) ms in the control group (P < 0.001, t-test). There were no significant differences in the prevalence of high blood pressure, diabetes or lipid profiles. However, patients on steroids had a higher mean QTD (S.E.): 63.5 (4) compared with 48 (2.7) ms in those patients who had not received long-term steroids (P=0.003, t-test). CONCLUSION: RA patients have an increased risk of subclinical vascular disease as was shown by a higher prevalence of carotid disease, peripheral arterial disease and increased QTD. Among traditional risk factors we found a history of steroid usage to be one of the potential risk factors.

Diphenylcyclopropenone (diphencyprone, DPCP) in the treatment of chronic severe alopecia areata (AA).

BACKGROUND: Diphenylcyclopropenone (DPCP) has been reported to be an effective topical immunotherapy of extensive alopecia areata (AA) with highly variable reported results. OBJECTIVE: The purposes of this study were to assess the efficacy, side effects, and adverse prognostic factors in the treatment of alopecia areata with DPCP. METHODS: 21 patients were included in the study with chronic and extensive AA. Patients were sensitized in the beginning with 2% DPCP, and the concentrations were increased gradually beginning with 0.000001% every one to two weeks for a period of 6 months. RESULTS: 15 patients (71.4%) had a complete or partial recovery at the end of the treatment period. Most frequent side effects were erythema at the site of application, pigmentation, and lymph node enlargement. The most important adverse prognostic factors were duration of AA, history of atopy, and presence of nail changes. CONCLUSION: Treatment of AA with topical DPCP is effective. Though the treatment may have some side effects, in most cases they are tolerable and respond well to treatment.

Activated factor XII in rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with premature mortality, with approximately 50% of deaths being due to cardiovascular disease. It has been shown that the increased incidence of cardiovascular disease is independent of traditional risk factors. Previous studies have shown an increased risk of coronary heart disease with increased levels of activated factor XII (FXIIa). The aim of this study was to investigate levels of FXIIa in patients with RA. We studied 32 patients with RA and 30 age- and sex-matched control subjects. We found FXIIa levels significantly increased in the patient group, with 56% of the patients and 6.7% of controls having levels greater than or equal to 2 ng/ml. A previous study has shown that individuals with levels of 2 ng/ml or more have an increased risk of coronary heart disease. Measurement of FXIIa could perhaps help to identify an 'at risk' group of patients, allowing early intervention therapy.