Shorter sleep duration is associated with poorer glycemic control in type 2 diabetes patients with untreated sleep-disordered breathing

Purpose

The purpose of this study is to explore the impact of sleep duration on glycemic control in type 2 diabetes patients with untreated sleep-disordered breathing (SDB).

Methods

Ninety type 2 diabetes patients participated in the study. SDB was diagnosed using an overnight in-home monitoring device (WatchPAT200). Sleep duration was recorded by wrist actigraphy for 7 days. Medical records were reviewed for hemoglobin A1c (HbA1c) values.

Results

Seventy-one patients (78.8 %) were diagnosed with SDB [apnea-hypopnea index (AHI) ≥ 5]. In patients with SDB, there was no significant relationship between AHI and glycemic control. In addition, oxygen desaturation index, minimum oxygen saturation, and time spent below oxygen saturation of 90 % were not significantly correlated with glycemic control. Sleep duration, however, was inversely correlated with HbA1c (r = ?0.264, p 0.026). Multiple regression analysis adjusting for age, sex, body mass index, insulin use, diabetes duration, and AHI revealed that sleep duration was significantly associated with HbA1c (p = 0.005). Each hour reduction in sleep duration was associated with a 4.8 % increase in HbA1c of its original value (95 % CI 1.5–8.0).

Conclusion

In type 2 diabetes patients with untreated SDB, shorter sleep duration was independently associated with poorer glycemic control. Sleep duration optimization may lead to improved glycemic control in this population.

     

Anti-inflammatory activity of methanolic extracts from Ventilago harmandiana Pierre

Methanolic extracts from the heart wood, stem bark, and stem wood of Ventilago harmandiana Pierre (Family Rhamnaceae) were assessed for anti-inflammatory effects using both acute and chronic inflammatory models. Analgesic and antipyretic activities of the extracts were also evaluated. It was found that all extracts possessed strong inhibitory effects on the acute phase of inflammation as seen in ethyl phenylpropiolate (EPP)- and arachidonic acid (AA)-induced ear edema as well as in carrageenin-induced paw edema in rats. The extracts elicited only weak inhibitory activity on cotton pellet-induced granuloma formation, a subchronic inflammatory model. In the analgesic test, all extracts exerted pronounced inhibitory activity in acetic acid-induced writhing response but showed only weak effects in the tail-flick test. The extracts also showed excellent antipyretic activity on yeast-induced hyperthermia in rats.     

Constituents of the leaves and twigs of Ficus hispida

A new norisoprenoid, ficustriol (1), and the known phenanthroindolizidine alkaloid O-methyltylophorinidine (2), were isolated from a CHCl3 extract of the leaves and twigs of Ficus hispida. O-Methyltylophorinidine showed potent cytotoxic activity when tested against a small panel of human cancer cells, while ficustriol was inactive. The structure and stereochemistry of 1 were determined using chemical and spectral methods.     

Analgesic,anti-inflammatory and venotonic effects of Cissus quadrangularis Linn.

Cissus quadrangularis, a medicinal plant indigenous to Asia and Africa, is used for many ailments, especially for the treatment of hemorrhoid. The effects associated with hemorrhoid, i.e. analgesic and anti-inflammatory activities as well as the venotonic effect of the methanol extract of C. quadrangularis (CQ) were assessed in comparison with reference drugs. In the analgesic test, CQ provoked a significant reduction of the number of writhes in acetic acid-induced writhing response in mice. CQ also significantly reduced the licking time in both phases of the formalin test. The results suggest peripheral and central analgesic activity of CQ. In acute phase of inflammation CQ elicited the inhibitory effect on the edema formation of the rats’ ear induced by ethyl phenylpropiolate as well as on the formation of the paw edema in rats induced by both carrageenin and arachidonic acid. It is likely that CQ is a dual inhibitor of arachidonic acid metabolism. In addition, CQ exerted venotonic effect on isolated human umbilical vein similarly to the mixture of bioflavonoids, i.e. 90% diosmin and 10% hesperidin. The results obtained confirmed the traditional use of C. quadrangularis for the treatment of pain and inflammation associated with hemorrhoid as well as reducing the size of hemorrhoids.     

Involvement of P2X(7) purinergic receptor and MEK1/2 in interleukin-8 up-regulation by LL-37 in human gingival fibroblasts

Montreekachon P, Chotjumlong P, Bolscher JGM, Nazmi K, Reutrakul V, Krisanaprakornkit S. Involvement of P2X ₇ purinergic receptor and MEK1/2 in interleukin‐8 up‐regulation by LL‐37 in human gingival fibroblasts. J Periodont Res 2011; 46: 327–337.© 2011 John Wiley & Sons A/S Background and Objective: The antimicrobial peptide LL‐37, derived from human neutrophils, can directly chemoattract leukocytes and up‐regulate the expression of several immune‐related genes in various cell types. In this study, we wanted to determine the immunoregulatory effect of LL‐37 on interleukin‐8 (IL‐8) expression in human gingival fibroblasts (HGFs) and to characterize intracellular signaling pathway(s) and receptor(s) involved in IL‐8 induction. Material and Methods: Cultured fibroblasts were treated with different concentrations of LL‐37 or interleukin‐1β (IL‐1β), as a positive control, for specific periods of time in the presence or absence of various inhibitors. RT‐PCR and real‐time PCR were conducted to analyze the expression of IL‐8 mRNA, and the IL‐8 levels in cell‐free culture media were measured using ELISAs. The MTT assay was performed to determine the cytotoxicity of LL‐37. Results: Nontoxic concentrations of LL‐37 (up to 10 μm ) and IL‐1β significantly up‐regulated the expression of IL‐8 mRNA in a dose‐dependent manner (p < 0.05). The IL‐8 protein levels were consistently significantly elevated in conditioned media of LL‐37‐treated HGFs (p < 0.05). IL‐8 up‐regulation by LL‐37 was completely abrogated by 20 μm U0126, consistent with transient phosphorylation of p44/42 MAP kinases. Moreover, pretreatment with Brilliant Blue G (a selective antagonist of the P2X₇ receptor) and the neutralizing antibody against P2X₇ blocked IL‐8 up‐regulation in a dose‐dependent manner, consistent with expression of the P2X₇ receptor in HGFs. Conclusion: These findings indicate that LL‐37 induces IL‐8 expression via the P2X₇ receptor and the MEK1/2‐dependent p44/42 MAP kinases in HGFs, suggesting both direct and indirect involvement of LL‐37 in neutrophil recruitment into an inflammatory site within diseased periodontal tissues.     

Anti-inflammatory, analgesic and antipyretic activities of the extract of gamboge from Garcinia hanburyi Hook f

In Thai folklore medicine, gamboge, the yellow gum-resin secreted from Garcinia hanburyi, is used for infected wound, pain and edema The ethyl acetate extract from Garcinia hanburyi (GH5763) was assessed for anti-inflammatory, analgesic and antipyretic activities using experimental animal models. It was found that GH5763 possessed inhibitory activity on acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema and carrageenin-induced hind paw edema in rats. However, GH5763 did not elicit any inhibitory effect on arachidonic acid-induced hind paw edema. In subchronic inflammatory model, GH5763 provoked a significant reduction of both transudative and proliferative phase when tested on cotton pellet-induced granuloma model. GH5763 also reduced the alkaline phosphatase activity in serum of rats in this animal model. In the analgesic test, GH5763 elicited inhibitory activity on acetic acid-induced writhing response and on both the early and the late phase of formalin test. Moreover, GH5763 also possessed an excellent antipyretic effect when tested in yeast-induced hyperthermic rats. It is postulated that the anti-inflammatory, analgesic and antipyretic activities of GH5763 are caused by the inhibition of the prostaglandin biosynthesis.     

Search for abnormalities of nuclear corepressors, coactivators, and a coregulator in families with resistance to thyroid hormone without mutations in thyroid hormone receptor beta or alpha genes

The syndrome of resistance to thyroid hormone (RTH) is characterized by decreased tissue responsiveness to thyroid hormones. Inheritance is usually autosomal dominant due to mutations in the ligand-binding domain or adjacent hinge region of the thyroid hormone receptor beta (TRbeta) gene. Six of 65 families with the RTH phenotype studied in our laboratory had normal TRbeta1 and TRbeta2 gene sequences. Their clinical characteristics were not different from those of subjects with TRbeta gene mutations. Four of the 6 families were amenable to linkage analysis, and TRalpha involvement was excluded. Candidate genes were then evaluated for their possible involvement in the RTH phenotype in these 4 families: 2 coactivators [NCoA-1 (SRC-1) and NCoA-3 (AIB-1)], 2 corepressors (NCoR and SMRT), and a coregulator (RXRgamma). DNA was obtained from 8 affected subjects and 41 of 45 living first degree relatives. In 2 of the 4 families, the mode of inheritance could be determined by pedigree analysis and was found to be autosomal dominant. Linkage analyses were performed using polymorphic markers near or within the 5 candidate genes. When analyses were not informative or linkage could not be excluded, direct sequencing of the genes in question was performed. Involvement of NCoA-1 was excluded in all four families assuming autosomal dominant inheritance. Roles for NCoR, SMRT, and NCoA-3 were excluded in three and a role for RXRgamma was excluded in two of the four families. However, if the two families without proven dominant mode of inheritance were compound heterozygous, only the involvement of NCoA-1 could be excluded in both. Roles for NCoR, SMRT, and RXRgamma were excluded in one of these two families. Thus, NCoA-1 and RXRgamma genes were not found to be the cause of RTH in subjects without TR gene mutations even though the absence of NCoA-1 and RXRgamma is the cause of RTH in mice. Involvement of other candidate genes in the mediation of thyroid hormone action as well as intracellular hormone transport needs to be explored in these families with non-TRbeta, TRalpha RTH.     

Diabetes in Thailand: Status and Policy

Like other countries in the Western Pacific region, Thailand is facing increasing numbers of patients with diabetes due to unhealthy diets, high obesity rates, and an aging society. Diabetes is a considerable burden for developing countries as it reduces quality of life, increases mortality, and drives up healthcare costs. The disease detection rate in Thailand has improved in recent years, but glycemic control remains suboptimal and significant numbers of patients suffer from complications. Universal healthcare coverage has increased access to care, but inequality exists between different health plans and non-medication diabetes supplies are not yet widely covered. Diabetes self-management education has not yet been standardized and a multidisciplinary team approach is not widely utilized. The Thai government recognizes the burden of diabetes and has launched nationwide programs of health promotion and disease prevention. In addition, local initiatives have targeted reductions in specific complications, including retinopathy and diabetic foot problems, which has resulted in better disease prevention and treatment. Along with strategic public health planning, increased collaboration between private and public sectors, enhanced professional training, increased use of technology and data management, and equitable distribution of care are all needed to improve outcomes of patients with diabetes in Thailand.     

Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide

We present an unusual variant of T(4)-binding globulin (TBG) found in a family from Allentown, Pennsylvania (TBG-AT). The heterozygous proposita presented serum total T(4) and TBG levels ranging from low to normal. TBG gene sequencing revealed a C-to-T substitution in codon -2 (CAC to TAC) leading to the substitution of the normal histidine by a tyrosine within the signal peptide. No mutation within the mature peptide was found. Allele-specific PCR confirmed the H(-2)Y mutation in the propositas mother and son. T(4)-binding analysis of TBG in serum from the proposita and son showed normal affinity but reduced capacity when compared with the unaffected father. Heat stability and isoelectric focusing of TBG-AT were normal. In vitro expression of a recombinant TBG-AT in Xenopus oocytes revealed a diminished secretory efficiency and confirmed the normal binding affinity and heat stability of the small amount of secreted TBG-AT. This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency.