Fatigue and oxidative stress response to physical activity in type 2 diabetic patients

Physical activity (PA) and exercise is known to have a positive impact on a variety of variables pertinent to diabetes and cardiovascular disease. The aims of this study were to investigate the effects of physical activity on fatigue scores, oxidative stress, and glycemic control variables of individuals with type 2 diabetes mellitus (T2DM). Seventy-five subjects diagnosed with T2DM for more than 5 years aged 18–65 years participated in this study. The participants classified according to energy expenditure into, physically inactive [≤500 metabolic equivalents (METs)-min/week, n?=?25], moderate PA (500–2500 METs-min/week, n?=?25), and PA (≥2500 METs-min/week, n?=?25). The Global Physical Activity Questionnaire (GPAQ) version 2.0 was used to classify physical activity. The multidimensional checklist individual strength questionnaire (CIS20r) was used to measure chronic fatigue. Blood glucose was measured using a glucose oxidase and peroxidase (GOD-POD) colorimetric method. HbA1c was measured using a commercial kit. Serum insulin level was determined using an ELISA. Analysis of oxidative stress parameters including malonaldehyde (MDA) and total antioxidant capacity (TAC) was done. To test differences between severely fatigued and healthy subjects, an independent t test was performed. Spearman correlations were used to assess correlations between fatigue severity score and disease-related and psychosocial factors. A level of significance was set at p?<?0.05. The results showed a significant reduction of fasting blood sugar, glycosylated hemoglobin, fasting insulin, and MDA along with significant increase in TAC activity in the participants with moderate PA (P?<?0.05) and PA (P?<?0.01), respectively. In relation to CIS-fatigue measurements, about 33 % of the study population (n?=?25) had a CIS score above the cutoff score of 37 with 59.5 mean CIS score, and 67 % of the study population (n?=?50) had CIS score below the cutoff 37; they were classified into heightened fatigue (score 27–35) and healthy (score ≤27). There was a significant correlation between the reduction of diabetic related variables, BMI, PA status, and CIS-fatigue score analyses in T2DM patients. CIS-fatigue scores correlated positively with diabetic related variables and negatively with PA, BMI, and TAC activity. PA plays a vital role in improving CIS-fatigue score in type 2 diabetic patients via reducing oxidative stress and diabetic related variables.     

Antipyretic,anti-inflammatory and analgesic activity of <Emphasis Type="Italic">Acacia hydaspica</Emphasis> R. Parker and its phytochemical analysis

Background

Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles.

Methods

Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, ¹H NMR, ¹³C NMR and ²D NMR spectroscopic analyses, and also by comparison with reported literature.

Results

Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p?<?0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E₂ (PGE₂) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica.

Conclusion

These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

     

Development of mitral and tricuspid regurgitation in right ventricular apex versus right ventricular outflow tract pacing

Purpose

This study aimed at comparing the development of tricuspid and mitral regurgitation between the right ventricular outflow tract (RVOT) and right ventricular apex (RVA) pacing.

Methods

We prospectively enrolled 164 patients for permanent pacemaker implantation due to sick sinus syndrome or atrioventricular block and randomly divided them into two equal groups to receive either RVOT or RVA pacing. Patients with heart failure or valvular disease were excluded. The post-procedural echocardiographic evaluations were performed 1 year after the pre-procedural echocardiography, and the results were compared with respect to the development of mitral and tricuspid regurgitation and probable changes in the ejection fraction (EF).

Results

Age, gender, pacing mode, and baseline cardiac rhythm did not significantly differ between the RVOT and RVA pacing groups. The incidence of mitral regurgitation was significantly higher in the RVA group (p?=?0.03), but the incidence of tricuspid regurgitation was similar in both groups. There was a trend toward less tricuspid regurgitation in the RVOT group; however, it was not statistically significant. The mean EF was not significantly different between the study groups.

Conclusion

It seems that the incidence of mitral regurgitation in RVA pacing is significantly higher than that in RVOT pacing. The formation of tricuspid regurgitation needs to be discussed in the future.

Clinical trial registration number

IRCT201103146061N1     

Chlorophyll derivatives can be an efficient weapon in the fight against dengue

Dengue, a mosquito-borne viral infection, is one of the major public health concerns in the tropical and subtropical regions of the world. Approximately, 2.5 billion people across the world are at risk from dengue and 50 to 100 million new infections of dengue occur annually. There is yet no vaccine or medicine available against dengue, and treatment remains only supportive. Targeting its vector by a combination of biological and chemical approaches and management of breeding sites are currently the only existing approaches to control or eliminate dengue. Chlorophyll derivatives like chlorophyllin and pheophorbide have been reported as effective natural photosensitizers against larvae of several insects including flies. Chlorophyll derivatives were also reported effective against larval stages of freshwater snails as well as against certain parasites of fish. This article briefly discusses the possible application of chlorophyll derivatives in controlling dengue vectors and hence the disease itself. Chlorophyll derivatives can prove to be a good contributor in an integrated approach against dengue.     

Mesoporous PbO nanoparticle-catalyzed synthesis of arylbenzodioxy xanthenedione scaffolds under solvent-free conditions in a ball mill

A protocol for the efficient synthesis of arylbenzodioxy xanthenedione scaffolds was developed via a one-pot multi-component reaction of aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and 3,4-methylenedioxy phenol using mesoporous PbO nanoparticles (NPs) as a catalyst under ball milling conditions. The synthesis protocol offers outstanding advantages, including short reaction time (60 min), excellent yields of the products (92–97%), solvent-free conditions, use of mild and reusable PbO NPs as a catalyst, simple purification of the products by recrystallization, and finally, the use of a green process of dry ball milling.

An efficient one-pot multicomponent protocol was developed for the synthesis of arylbenzodioxy xanthenedione scaffolds using mesoporous PbO nanoparticles as reusable catalyst under solvent-free ball milling conditions.

Recently, the ball milling technique has received great attention as an environmentally benign strategy in the context of green organic synthesis.^1a The process of “ball milling” has been developed by adding mechanical grinding to the mixer or shaker mills. The ball milling generates a mechanochemical energy, which promotes the rupture and formation of the chemical bonds in organic transformations.^1b Subsequently, detailed literature^1c and books on this novel matter have been published.^2a,b Several typical examples include carbon–carbon and carbon–heteroatom bond formation,^2c organocatalytic reactions,^2d oxidation by using solid oxidants,^2e dehydrogenative coupling, asymmetric, and peptide or polymeric material synthesis, which have been reported under ball milling conditions.^2e Hence, the organic reactions using ball milling activation carried out under neat reaction environments, exhibit major advantages,^2f including short reaction time, lower energy consumption, quantitatively high yields and superior safety with the prospective for more improvement than the additional solvent-free conditions and clear-cut work-up.^3–5On the other hand, the organic transformations using metal and metal oxide nanoparticles⁶ are attracting enormous interest due to the unique and interesting properties of the NPs.^7,8,9a Particularly, PbO NPs^9b provide higher selectivity in some organic reactions^9c and find applications in various organic reactions, like Paal–Knorr reaction,¹⁰ synthesis of diethyl carbonate,¹¹ phthalazinediones,¹² disproportionation of methyl phenyl carbonate to synthesize diphenyl carbonate,¹³ the capping agent in organic synthesis, and selective conversion of methanol to propylene.¹⁴ In addition, the PbO NPs are also used in many industrial materials.^15,16However, till date, PbO NPs have not been explored in MCRs leading to biologically important scaffolds. Among others, the xanthene scaffolds¹⁷ are one of the important heterocyclic compounds¹⁸ and are extensively used as dyes, fluorescent ingredients for visual imaging of the bio-molecules, and in optical device technology because of their valuable chemical properties.¹⁹ The xanthene molecules have conjointly been expressed for their antibacterial activity,²⁰ photodynamic medical care, anti-inflammatory drug impact, and antiviral activity. Because of their various applications, the synthesis of these compounds has received a great deal of attention.²¹ Similarly, vitamin K nucleus^22,23 shows a broad spectrum of biological properties, like anti-inflammatory, antiviral, antiproliferative, antifungal, antibiotic, and antipyretic.^24a As a consequence, a variety of strategies^24b have been demonstrated in the literature for the synthesis of xanthenes and their keto derivatives, like rhodomyrtosone-B,^25a rhodomyrtosone-I,^25b and BF-6 ^25c as well as their connected bioactive moieties. Few biologically active xanthene scaffolds are shown in (Fig. 1).Open in a separate windowFig. 1Some biologically important xanthenes and their keto derivatives.Due to the significance of these compounds, the synthesis of xanthenes and their keto derivatives using green protocols is highly desirable. Reported studies reveal that these scaffolds are synthesized by three-component condensations using p-TSA²⁶ and scolecite²⁷ as catalysts. However, these methods suffer from the use of toxic acidic catalysts like p-TSA, long reaction times (3 h), harsh refluxing²⁶ or microwave reaction conditions,²⁷ and tedious work-up procedures. The previously reported methods for the synthesis of xanthenediones are shown in Scheme 1.Open in a separate windowScheme 1Previous protocol for the synthesis of xanthenedione derivatives.Herein, we report an economical and facile multicomponent protocol, using ball milling, for the synthesis of 7-aryl-6H-benzo[H][1,3]dioxolo[4,5-b]xanthene-5,6(7H)-dione using PbO NPs as a heterogeneous catalyst (Scheme 2). The PbO NPs are non-corrosive, inexpensive, and easily accessible.Open in a separate windowScheme 2General reaction scheme of PbO NP-catalyzed synthesis of the xanthenedione scaffolds under ball milling conditions.In our protocol,²⁸ the PbO NPs were initially prepared by mixing sodium dodecyl sulphate (2.5 mmol) and sodium hydroxide (10 mL, 0.1 N) with an aqueous methanolic solution of lead nitrate (2 mmol) under magnetic stirring at 30 °C by continuing the reaction for 2 h. Then, the obtained white polycrystalline product was filtered, washed with H₂O, and dried at 120 °C, followed by calcination at 650 °C for 2 h. During this step, the white PbO NPs turned pale yellow in colour. Eventually, the synthesized PbO was then characterized by spectroscopic and analytical techniques.The powder X-ray diffraction (XRD) pattern revealed the crystalline nature of the PbO NPs as the diffraction peaks corresponding to (131), (311), (222), (022), (210), (200), (002), and (111) crystal planes were identified (Fig. 2). The XRD outline of the synthesized PbO NPs was further established for the formation of space group Pca2₁ ²⁹ with a single orthorhombic structure (JCPDS card number 76-1796). The sharp diffraction peaks indicated good crystallinity, and the average particle size of the PbO NPs was estimated to be 69 nm, as calculated using the Debye–Scherer equation.Open in a separate windowFig. 2The powder XRD pattern of PbO NPs.The surface morphology of the PbO NPs was analyzed by scanning electron microscopy (SEM), and the SEM image revealed the discrete and spongy appearance of the PbO NPs (Fig. 3).Open in a separate windowFig. 3The SEM image of PbO NPs.Moreover, the elemental composition obtained from energy dispersive X-ray (EDX) analysis confirmed that the material contains Pb and O elements, and no other impurity was present (Fig. 4).Open in a separate windowFig. 4The EDAX spectrum of crystalline PbO NPs.The transmission electron microscopy (TEM) image shown in Fig. 5 indicated the formation of orthorhombic crystallites of PbO with several hexagon-shaped particles. The dark spot in the TEM micrograph further confirmed the synthesis of PbO NPs, as the selected area diffraction pattern associated with such spots reveals the occurrence of the PbO NPs in total agreement with the X-ray diffraction data (Fig. 6). The average size of the PbO nanocrystals by TEM was approximated to be around 20 nm.Open in a separate windowFig. 5The TEM image of nanocrystalline PbO NPs.Open in a separate windowFig. 6The SAED image of nanocrystalline PbO NPs.The Fourier transform infrared (FT-IR) spectrum (ESI, S6^†) of the PbO NPs displayed peaks at 575, 641, and 848 cm⁻¹, which corresponds to the Pb–O vibrations. Furthermore, the absorption band at ∼3315 cm⁻¹ was due to the presence of the hydroxyl group (–OH) in the NPs.The N₂ adsorption–desorption isotherms of the PbO nanoparticles shown in Fig. 7 was consistent with type IV adsorption–desorption isotherms with H1 hysteresis corresponding to the cylindrical mesoporous structure. Moreover, the surface area, pore-volume, and BJH pore diameter were found to be 32.0 m² g⁻¹, 0.023 cm³ g⁻¹, and 30.9 Å, respectively.Open in a separate windowFig. 7BET surface area and pore size of nanocrystalline PbO catalyst.The catalytic activity of the synthesized PbO NPs was tested in a one-pot multicomponent synthesis of arylbenzodioxoloyl xanthenedione derivative under ball milling condition according to the reaction scheme 2a, with 3,4-dimethoxybenzaldehyde (166.2 mg, 1.0 mmol), 3,4-methylenedioxyphenol (138.0 mg, 1.0 mmol), and 2-hydroxy-1,4-naphthoquinone (174.0 mg, 1.0 mmol) as reactants. The reaction conditions, the ball milling parameters (speed, time, and ball to solids ratio), and the PbO nanocatalyst amount were first optimized to produce the highest yield using experimental design as shown in

Intra-night variation in apnea-hypopnea index affects diagnostics and prognostics of obstructive sleep apnea

Sleep and Breathing - Diagnostics of obstructive sleep apnea (OSA) is based on apnea-hypopnea index (AHI) determined as full-night average of occurred events. We investigate our hypothesis that...