Acupuncture and moxibustion in the treatment of ulcerative colitis: a randomized controlled study

OBJECTIVE: Acupuncture has traditionally been used in the treatment of inflammatory bowel disease in China and is increasingly applied in Western countries. The objective of this study was to investigate the efficacy of acupuncture and moxibustion in the treatment of active ulcerative colitis (UC). MATERIAL AND METHODS: In a prospective, randomized, controlled clinical trial 29 patients with mild to moderately active UC (mean age 37.8 +/- 12.0 years) were randomly assigned to receive either traditional acupuncture and moxa (TCM group, n = 15), or sham acupuncture consisting of superficial needling at non-acupuncture points (control group, CG, n = 14). All patients were treated in 10 sessions over a period of 5 weeks and followed-up for 16 weeks. The main outcome measure was the change in the Colitis Activity Index (CAI) after treatment; secondary outcome measures were changes in quality of life, general well-being and serum markers of inflammation. RESULTS: In the TCM group, the CAI decreased from 8.0 (+/- 3.7) to 4.2 (+/- 2.4) points and in the control group from 6.5 (+/- 3.4) to 4.8 (+/- 3.9) points (TCM versus CG: p = 0.048). In both groups these changes were associated with significant improvements in general well-being (TCM group: from 3.0 (+/- 1.8) to 1.8 (+/- 1.0); CG: from 3.2 (+/- 1.9) to 2.2 (+/- 1.7)) and quality of life (TCM group: from 146 (+/- 23) to 182 (+/- 18); CG: from 157 (+/- 20) to 183 (+/- 23)). No significant differences between the TCM and CG were found regarding these secondary outcome measures. CONCLUSIONS: Differences in efficacy between traditional acupuncture and sham acupuncture were small and significant only for CAI as the main outcome measure. Both traditional and sham acupuncture seem to offer an additional therapeutic benefit in patients with mild to moderately active UC.     

Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes

The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 (GLP-1) is not established. Here, the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 (DPP-4) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [age: 65 +/- 8 yr (SD), body mass index: 27.3 +/- 3.3 kg/m(2), fasting plasma glucose: 9.0 +/- 1.3 mmol/liter]. Compared with placebo (n = 19), a specific DPP-4 inhibitor [(1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine) (LAF237); 100 mg daily, n = 18] reduced fasting glucose by 0.70 mmol/liter (P = 0.037), 4-h prandial glucose excursion by 1.45 mmol/liter (P < 0.001), and mean 24-h glucose by 0.93 mmol/liter (P < 0.001). Baseline and postprandial active GLP-1 were increased by LAF237. The glucagon response to breakfast was reduced by LAF237 (glucagon levels at 60 min were 88 +/- 8 pg/ml before treatment vs. 77 +/- 5 pg/ml after; P = 0.001). In contrast, the overall insulin levels were not altered. The 4-wk reduction in glucagon correlated with the reduction in 2-h glucose (r = 0.61; P = 0.008). No such association was observed for insulin. Thus, improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels.     

Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

Aims/hypothesis We assessed the effects of vildagliptin, a novel dipeptidyl peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in patients with type 2 diabetes.Subjects, materials and methods This was a single-centre, randomised, double-blind study in drug-naive patients with type 2 diabetes. Patients received vildagliptin (50 mg twice daily, n=15) or placebo (n=16) for 4 weeks. Triglyceride, cholesterol, lipoprotein, glucose, insulin, glucagon and glucagon-like peptide-1 (GLP-1) responses to a fat-rich mixed meal were determined for 8 h postprandially before and after 4 weeks of treatment.Results Relative to placebo, 4 weeks of treatment with vildagliptin decreased the AUC_0–8h for total trigyceride by 22±11% (p=0.037), the incremental AUC_0–8h (IAUC_0–8h) for total triglyceride by 85±47% (p=0.065), the AUC_0–8h for chylomicron triglyceride by 65±19% (p=0.001) and the IAUC_0–8h for chylomicron triglyceride by 91±28% (p=0.002). This was associated with a decrease in chylomicron apolipoprotein B-48 (AUC_0–8h, −1.0±0.5 mg l⁻¹ h, p=0.037) and chylomicron cholesterol (AUC_0–8h, −0.14±0.07 mmol l⁻¹ h, p=0.046). Consistent with previous studies, 4 weeks of treatment with vildagliptin also increased intact GLP-1, suppressed inappropriate glucagon secretion, decreased fasting and postprandial glucose, and decreased HbA_1c from a baseline of 6.7% (change, −0.4±0.1%, p<0.001), all relative to placebo.Conclusions/interpretation Treatment with vildagliptin for 4 weeks improves postprandial plasma triglyceride and apolipoprotein B-48-containing triglyceride-rich lipoprotein particle metabolism after a fat-rich meal. The mechanisms underlying the effects of this dipeptidyl peptidase IV inhibitor on postprandial lipid metabolism remain to be explored.     

Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

ABM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ(PPARγ) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas. METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined, Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS: Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the over-expression of HSP70. PPARγ ligands could represent a new therapeutic option in the treatment of AP.     

Pharmacokinetics,biocompatibility and bioavailability of a controlled release monoclonal antibody formulation

The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs). In order to further investigate their applicability, a single-dose animal study was conducted to compare the biocompatibility, the pharmacokinetics and the bioavailability of a human monoclonal antibody liquid formulation with two alginate-based sustained delivery systems after subcutaneous administration in rats. 28 days after injection, the depot systems were still found in the subcutis of the animals. A calcium cross-linked alginate formulation, which was injected as a hydrogel, was present as multiple compartments separated by subcutaneous tissue. An in situ forming alginate formulation was recovered as a single compact and cohesive structure. It can be assumed that the multiple compartments of the hydrogel formulation led to almost identical pharmacokinetic profiles for all tested animals, whereas the compact nature of the in situ forming system resulted in large interindividual variations in pharmacokinetics. As compared to the liquid formulation the hydrogel formulations led to lower mAb serum levels, and the in situ forming system to a shift in the time to reach the maximum mAb serum concentration (T_max) from 2 to 4 days. Importantly, it was shown that after 28 days only marginal amounts of residual mAb were present in the alginate matrix and in the tissue at the injection site indicating nearly complete release. In line with this finding, systemic drug bioavailability was not affected by using the controlled release systems. This study successfully demonstrates the suitability and underlines the potential of polyanionic systems for local and controlled mAb delivery.     

Upper body movements in children with hemiplegic cerebral palsy walking with and without an ankle–foot orthosis

Background

It has previously been discussed that treatment of the hemiplegic arm in patients with cerebral palsy can improve gait parameters in the lower body. Our question was whether improving the ankle rocker with an orthosis has an effect on the upper body during walking. The main aim was to investigate, which trunk and arm kinematics of toe walking children with hemiplegic cerebral palsy are changed by wearing a hinged ankle–foot orthosis, restoring an initial heel contact.

Methods

Specific parameters of the pelvis, thorax, and arm kinematics were investigated. Differences in the hemiplegic side between the barefoot and the orthotic condition were calculated by Students t-tests. Additionally, the 95% confidence intervals were used to explore clinically relevant differences between the controls and the patients and asymmetries within the patients' affected and unaffected sides.

Findings

Pelvic tilt range of motion (barefoot: 7.5° (6.1–9.0°), orthosis: 6.6° (5.1–8.1) P = 0.040) and mean shoulder abduction (barefoot: 14.3° (10.2–18.4°), orthosis: 12.1° (8.4–15.8) P = 0.027) were the only two parameters with statistically significant differences, although not clinically relevant, between the barefoot and orthotic conditions. Abnormalities in all three planes were explored between the patients and controls. The entire trunk was more externally rotated, the pelvis stood lower, and the elbow was more flexed on the hemiplegic side compared to the unaffected side.

Interpretation

A hinged ankle–foot orthosis, restoring the first ankle rocker, had no clinically relevant effects on trunk kinematics. None of the observed upper body gait deviations seemed to be secondary to or caused by toe walking.     

Comparison of ultrasonography, intravenous pyelography and cystoscopy in detection of urinary tract lesions due to Schistosoma haematobium

The use of ultrasound in detecting urinary tract alterations by Schistosoma haematobium such as hydronephrosis and bladder calcifications was studied in 125 patients of the out-patients department of a district hospital in SE Tanzania, in an area highly endemic for this disease. Ultrasound was compared with plain abdominal X-ray (in 33 patients), intravenous pyelography (29), cystoscopy (31) and simple urine examination (125). Except for bladder calcifications which could not be demonstrated other than by X-ray, sonography compared favorably with IVP and cystoscopy and proved therefore to be a valuable tool in assessing S.h. related morbidity. In children moderate and advanced hydronephrosis were always associated with an irregular bladder wall and correlated strongly with the prevalence and intensity of S.h. infections as well as with haematuria and proteinuria. Important congestive pathology was observed in 1 out of 10 infected children and in 1 out of 20 examined adults.     

In vivo [31P]NMR studies on the influence of age on rat brain hypoxia

In this paper the response of cerebral phosphate metabolism to mild hypoxia in young, medium and old rats has been studied via in-vivo [31P]nuclear magnetic resonance (NMR). It was found that the young adults (5-6 months) were more sensitive to this mild stress than either the mature adult (11-12 months) or senescent (23-24 months) rats even though the depth of hypoxia (paO2 = 45-55 mm Hg) was equal for all age groups. They displayed an earlier onset of acidosis, a greater fall in PCr and larger rise in Pi. This response is presumably an attempt to maintain adequate adenosine triphosphate (ATP) levels via anaerobic glycolysis. In contrast, mature adults and senescent adults appear to be able to maintain ATP levels by increasing mitochondrial rates. Acidosis is less severe as are drops in PCr and rises in Pi. Recovery is less complete for the young rats: Pi levels remain high while PCr and pHi levels stay low after normoxia has been reinstigated. All metabolite levels in the mature and senescent adults return to within 10% of control levels. All the data were analyzed and differences were found to be statistically significant. This study reveals that, contrary to popular belief, mature and old rats respond more favorably to reduced O2 than younger individuals. This is due to a more severe anaerobic acidosis in the latter age group. Speculations to explain this disparity are based on the fact that previous in-vitro studies involve systems that are totally or partially disconnected from the organism will not account for important feedback control present in an in-vivo system as studied here.