METHODS: This study describes the formulation design, optimisation, characterisation and evaluation of insulin concentration via oral delivery in rats. A reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated to quantify insulin concentration in rat plasma. The proposed method produced a linear response over the concentration range of 0.39 to 50 µg/ml.
RESULTS: In vitro release study showed that dissolution of insulin in simulated gastric juice of pH 1.2 was prevented by alginate core and chitosan coating but rapidly released in simulated intestinal fluid (pH 6.8). Additionally, Formulation 3 (F3) has a particle size of 340.40 ± 2.39 nm with narrow uniformity exhibiting encapsulation efficiency (EE) of 72.78 ± 1.25 % produced highest absorption profile of insulin with a bioavailability of 40.23 ±1.29% and reduced blood glucose after its oral administration in rats.
CONCLUSION: In conclusion, insulin oral delivery system containing alginate and chitosan as a coating material has the ability to protect the insulin from enzymatic degradation thus enhance its absorption in the intestine. However, more work should be done for instance to involve human study to materialise this delivery system for human use.
OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.
SEARCH METHODS: We used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings.
SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence).
AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding findings should be interpreted with caution.Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.
METHODS: Sodium nitrite (50mg/L) was given to angiotensin II-infused hypertensive C57BL/6J (eight to ten weeks old) mice for two weeks in the drinking water. Arterial systolic blood pressure was measured using the tail-cuff method. Vascular responsiveness of isolated aortae and renal arteries was studied in wire myographs. The level of nitrite in the plasma and the cyclic guanosine monophosphate (cGMP) content in the arterial wall were determined using commercially available kits. The production of reactive oxygen species (ROS) and the presence of proteins (nitrotyrosine, NOx-2 and NOx-4) involved in ROS generation were evaluated with dihydroethidium (DHE) fluorescence and by Western blotting, respectively.
RESULTS: Chronic administration of sodium nitrite for two weeks to mice with angiotensin II-induced hypertension decreased systolic arterial blood pressure, reversed endothelial dysfunction, increased plasma nitrite level as well as vascular cGMP content. In addition, sodium nitrite treatment also decreased the elevated nitrotyrosine and NOx-4 protein level in angiotensin II-infused hypertensive mice.
CONCLUSIONS: The present study demonstrates that chronic treatment of hypertensive mice with sodium nitrite improves impaired endothelium function in conduit and resistance vessels in addition to its antihypertensive effect, partly through inhibition of ROS production.
MATERIALS AND METHODS: A total of 231 OSMF patients were selected and treated with basic regime including topical corticosteroids, oral antioxidants and the icecream-stick exercise regime and allotted randomly to two equal groups A and B. Group-A patients were additionally given MED. Subgroups A1 and B1 patients with an inter-incisal distance (IID) 20-35mm were not given any additional therapy; subgroup A2 and B2 patients (IID 20-35mm) were treated additionally with intra-lesional injections. Subgroups A3 and B3 with IID<20mm were managed surgically. IID was measured at baseline and at 6 months recall. The change in IID measurements was calculated and statistically analyzed using 2-way ANOVA and Tukeys multiple post hoc analysis.
RESULTS: Average improvement in IID after six months of recall visits was observed to be 8.4 mm in subgroup-A1 (n-53) compared to 5.5 mm in B1(n-50) (p<0.01). The IID improvement in subgroup-A2 was found to be 9.3mm (n-46) compared to 5.1 mm in B2 (n-48) (p<0.01). In the surgery group, mouth opening improvement was observed to be 9.6 mm in subgroup A3 (n-18) compared to 4.8 mm for B3 (n-16) (p<0.01).
CONCLUSIONS: Use of the MED appears to be effective for increasing oral opening in OMSF patients in conjunction with local, injection and/or surgical treatment.
METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire.
RESULTS: A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P<0.0001) was found for lower limb discomfort (-3.33 cm for MPFF 1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg).
CONCLUSIONS: MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.
MATERIAL AND METHODS: This was a five-year retrospective open cohort study using secondary data from the National Diabetes Registry. The study setting was all public health clinics (n = 47) in the state of Negeri Sembilan, Malaysia. Time to treatment intensification was defined as the number of years from the index year until the addition of another oral antidiabetic drug or initiation of insulin. Life table survival analysis based on best-worst case scenarios was used to determine the time to treatment intensification. Discrete-time proportional hazards model was fitted for the factors associated with treatment intensification.
RESULTS: The mean follow-up duration was 2.6 (SD 1.1) years. Of 7,646 patients, the median time to treatment intensification was 1.29 years (15.5 months), 1.58 years (19.0 months) and 2.32 years (27.8 months) under the best-, average- and worst-case scenarios respectively. The proportion of patients with treatment intensification was 45.4% (95% CI: 44.2-46.5), of which 34.6% occurred only after one year. Younger adults, overweight, obesity, use of antiplatelet medications and poorer HbA1c were positively associated with treatment intensification. Patients treated with more oral antidiabetics were less likely to have treatment intensification.
CONCLUSION: Clinical inertia is present in the management of T2D patients in Malaysian public health clinics. We recommend further studies in lower- and middle-income countries to explore its causes so that targeted strategies can be developed to address this issue.
CASE DESCRIPTION: A 28-year-old gentleman with body mass index of 34.3 was referred to us for management of double vision of 2 weeks duration. His symptom started after a brief episode of upper respiratory tract infection. His best corrected visual acuity was 6/6 OU. He had bilateral sixth nerve palsy worse on the left eye and bilateral hypometric saccade. His deep tendon reflexes were found to be hyporeflexic in all four limbs. No sensory or motor power deficit was detected, and his gait was normal. Plantar reflexes were downwards bilaterally and cerebellar examination was normal. Both optic discs developed hyperaemia and swelling. Magnetic resonance imaging of brain was normal and lumbar puncture revealed an opening pressure of 50 cmH2O. Anti-GQ1b IgG and anti-GT1a IgG antibody were tested positive.
CONCLUSION: Acute ophthalmoparesis without ataxia can present with co-occurrence of raised intracranial pressure. It is important to have a full fundoscopic assessment to look for papilloedema in patients presenting with Miller Fisher syndrome or acute ophthalmoparesis without ataxia.