The relationship between thyroid function,serum monokine induced by interferon gamma and soluble interleukin‐2 receptor in thyroid autoimmune diseases

Interactions between cytokines play an important role in the development of thyroid autoimmunity. Using enzyme-linked immunosorbent assay we investigated serum concentrations of soluble interleukin-2 receptor (sIL-2R), interferon-gamma, tumour necrosis factor (TNF)-α, interleukin (IL)-10, CD30, monokine induced by interferon-gamma (MIG), cytotoxic T lymphocyte antigen-4 and markers of apoptosis decoy receptor 3 and Bcl-2 in 28 patients with hyperthyroid Graves'' disease (GD), 24 patients with untreated Hashimoto''s thyroiditis (HT) and 15 healthy controls. TNF-α, IL-10 and sIL-2R were higher in GD compared with HT and controls (TNF-α: 8·79 in GD versus 2·54 pg/ml in HT, P = 0·01; IL-10: 10·00 versus 3·10 versus 3·10 pg/ml, P₁ < 0·001, P₂ = 0·005; sIL-2R: 1·26 versus 0·64 versus 0·46 ng/ml, P < 0·001). MIG and CD30 were higher in HT compared with controls (649·22 ± 262·55 versus 312·95 ± 143·35 pg/ml, P = 0·037, 6·57 ± 2·35 versus 3·03 ± 1·04 U/ml, P = 0·036 respectively). In GD sIL-2R decreased when the euthyroid state was achieved (1·31 ± 0·64 versus 0·260 ± 0·11, n = 12, P < 0·001). sIL-2R correlated positively with free thyroxine (FT4) (R = 0·521, P = 0·000) and negatively with thyroid stimulating hormone (TSH) (R = −0·472, P = 0·00132). MIG correlated negatively with FT4 (R = −0·573, P = 0·00234) and positively with TSH (R = 0·462, P = 0·0179). The results suggest that serum concentrations of sIL-2R and MIG are related to thyroid function rather than to activation of autoimmunity.     

Interferon regulatory factor 3 as key element of the interferon signature in plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel genetic associations in the Mexican mestizo population

Many genetic studies have found an association between interferon regulatory factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE); however, specific dendritic cell (DC) alterations have not been assessed. The aim of the present study was to address the expression of IRF3 and IRF5 on different DC subsets from SLE patients, as well as their association with interferon (IFN)-α production and novel SNPs. For the genetic association analyses, 156 SLE patients and 272 healthy controls from the Mexican mestizo population were included. From these, 36 patients and 36 controls were included for functional analysis. Two IRF3 SNPs − rs2304206 and rs2304204 – were determined. We found an increased percentage of circulating pDC in SLE patients in comparison to controls (8·04 ± 1·48 versus 3·35 ± 0·8, P = 0·032). We also observed enhanced expression of IRF3 (64 ± 6·36 versus 36·1 ± 5·57, P = 0·004) and IRF5 (40 ± 5·25 versus 22·5 ± 2·6%, P = 0·010) restricted to this circulating pDC subset from SLE patients versus healthy controls. This finding was associated with higher IFN-α serum levels in SLE (160·2 ± 21 versus 106·1 ± 14 pg/ml, P = 0·036). Moreover, the IRF3 rs2304206 polymorphism was associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence interval (CI) = 2·401 (1·187–4·858), P = 0·021] as well as enhanced levels of serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings suggest that the predominant IRF3 expression on circulating pDC is a key element for the increased IFN-α activation based on the interplay between the rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican mestizo SLE patients.     

Brine Shrimp Toxicity Evaluation of Some Tanzanian Plants Used Traditionally for the Treatment of Fungal Infections

Plants which are used by traditional healers in Tanzania have been evaluated to obtain preliminary data of their toxicity using the brine shrimps test. The results indicate that 9 out of 44 plant species whose extracts were tested exhibited high toxicity with LC₅₀ values below 20µg/ml. These include Aloe lateritia Engl. (Aloaceae) [19.1µg/ml], Cassia abbreviata Oliv. (Caesalpiniaceae) [12.7µg/ml], Croton scheffleri Pax (Euphorbiaceae) [13.7µg/ml], Hymenodactyon parvifolium Brig (Rubiaceae) [13.4µg/ml], Kigelia Africana L. (Bignoniaceae) [7.2µg/ml], and Ocimum suave Oliv. (Labiatae) [16.7µg/ml]. Twelve plants gave LC₅₀ values between 21 and 50µg/ml, 11 plants gave LC₅₀ values between 50 and 100 µg/ml, and 18 plants gave LC₅₀ values greater than 100 µg/ml.     

Tumour necrosis factor‐α plus interleukin‐10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients

Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of −308 G < A tumour necrosis factor (TNF)-α, −174 G > C interleukin (IL)-6 and −1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case–control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16–4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19–12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.     

In Vivo and In Vitro Effects of Bidens Pilosa L. (Asteraceae) Leaf Aqueous and Ethanol Extracts on Primed-Oestrogenized Rat Uterine Muscle

Bidens pilosa L. is an Asteraceae growing in tropical zones, and traditionally utilized worldwide in herbal medicine. The present work is based on its traditional use during child birth as a labour facilitator. In vivo tests of acute toxicity showed a weak toxic effect for both extracts but the toxicity of the ethanol extract (LD₅₀=6.15g/kg) was upper than that of the aqueous extract (LD₅₀=12.30g/kg). The three-days uterotrophic assay on immature mice showed body weight gain followed by a concentration-dependent decrease up to 4mg/g and a concentration dependent uterine wet weight increase. The ethanol extract exhibited the higher body weight gain representing 22.8±0.7%, (P≤0.001), at the concentration of 500µg/g/day, while the aqueous extract was significantly more efficient on the uterine wet weight gain of 0.24±0.001% (P≤0.05), at the concentration of 1000µg/g/day. In vitro isometric contraction measurement of oestrogen-primed rat uterine strips showed a significant high aqueous extract-induced contractile effect from 0.03–1.97mg/ml: on the amplitude of contraction (EC₅₀ = 0.44±0.10mg/ml, P≤0.05), and on the rate (1.21±0.25mg/ml, P>0.05). Inspite of the higher effect of the aqueous extract on the tonus (57.23±23%), the ethanol extract showed a high effect (EC₅₀=0.34±0.09mg/ml, P≤0.05). The weak toxicity, the estrogenic-like and the oxytocic-like activities observed could explain the empirical use of Bidens pilosa leaf aqueous extract as an uterotonic preparation to enhance labour, probably due to the presence of biologically active compound(s) which act directly on the uterine muscle.     

Antiproliferative Effect of Alcoholic Extracts of Some Gabonese Medicinal Plants on Human Colonic Cancer Cells

Extracts from Piptadeniastrum africanum Brenan (Mimosaceae), Petersianthus macrocarpus (Breauv) L. (Lecydaceae), Cissus debilis Planch (Vitaceae) and Dieffenbachia seguine Jacq. (Araceae) were tested in vitro for their antiproliferative activity on human colon cancer cell line (CaCo-2). The highest antiproliferative activities were obtained with the alcoholic extracts of the roots of Piptadeniastrum africanum (G-PAR), the leaves of Petersianthus macrocarpus (G-PMF) and the stem of Cissus debilis (G-CDL), with 50% inhibition concentrations (IC₅₀) of 15 µg/ml, 17 µg/ml and 25 µg/ml respectively. Only one extract (leaves of Dieffenbachia seguine (G-DSF)) exhibited weak antiproliferative activity with 50% inhibition concentration (IC₅₀) higher than 50 µg/ml.     

Response of BALB/c mice to a monovalent influenza A （H1N1） 2009 split vaccine

The novel influenza A (H1N1) 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A (H1N1) virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A (H1N1) split vaccine and evaluated its effects in BALB/c mice. Mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin (HA) alone or HA plus an aluminum hydroxide (Al(OH)₃) adjuvant. Immunization with varying doses of HA (3.75, 7.5, 15, 30, 45 or 60 µg) was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition (HI) and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses (0.5 ml containing 60 µg HA+600 µg Al(OH)₃ or 60 µg HA). Moreover, the vaccine was found to be safe at a dose of 120 µg HA+1200 µg Al(OH)₃ or 120 µg HA in 1.0 ml in rats. In conclusion, the present study provides support for the clinical evaluation of influenza A (H1N1) vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.     

Sweat Rates, Sweat Sodium Concentrations, and Sodium Losses in 3 Groups of Professional Football Players

Context:

Sweat sodium losses have never been reported in a large cohort of American football players.

Objective:

To compare sweat rates (SwtRs), sweat sodium concentrations (SwtNa⁺), and sodium losses in 3 groups of players (backs and receivers [BK], linebackers and quarterbacks [LB/QB], and linemen [LM]) to determine if positional differences and, therefore, size differences exist.

Design:

Observational study.

Setting:

Data were collected during practices in the second week of 2 consecutive training camps. The wet bulb globe temperature was 78.5°F ± 3.5°F (25.9°C ± 1.9°C).

Patients or Other Participants:

Eighteen BK, 12 LB/QB, and 14 LM volunteered.

Intervention(s):

Sterile sweat patches were applied to the right forearm after the skin was appropriately cleaned. The patches were removed during practice, placed in sterile tubes, centrifuged, frozen, and later analyzed by flame photometry.

Main Outcome Measure(s):

Sweat rate, SwtNa⁺, and sodium loss. We calculated SwtR by change in mass adjusted for urine produced and fluids consumed divided by practice time in hours.

Results:

Other than age, physical characteristics were different among groups (P < .001). The SwtR was different among groups (F_2,41  =  7.3, P  =  .002). It was lower in BK (1.42 ± 0.45 L/h) than in LB/QB (1.98 ± 0.49 L/h) (P < .05) and LM (2.16 ± 0.75 L/h) (P < .01), but we found no differences between SwtRs for LB/QB and LM. The SwtNa⁺ was not different among groups (BK  =  50 ± 16 mEq/L, LB/QB  =  48.2 ± 23 mEq/L, and LM  =  52.8 ± 25 mEq/L) and ranged from 15 to 99 mEq/L. Sweat sodium losses ranged from 642 mg/h to 6.7 g/h, and findings for group comparisons approached significance (P  =  .06). On days when players practiced 4.5 hours, calculated sodium losses ranged from 2.3 to 30 g/d.

Conclusions:

The BK sweated at lower rates than did the midsized LB/QB and large LM, but LB/QB sweated similarly to LM. Sweat sodium concentration and daily sodium losses ranged considerably. Heavy, salty sweaters require increased dietary consumption of sodium during preseason.     

Improved emergency myelopoiesis and survival in neonatal sepsis by caspase‐1/11 ablation

Over one million newborns die annually from sepsis with the highest mortality in premature and low-birthweight infants. The inflammasome plays a central role in the regulation of innate immunity and inflammation, and is presumed to be involved in protective immunity, in large part through the caspase-1-dependent activation of interleukin-1β (IL-1β) and IL-18. Studies in endotoxic shock, however, suggest that endogenous caspase-1 activity and the inflammasome contribute to mortality primarily by promoting excessive systemic inflammatory responses. We examined whether caspase-1 and the inflammasome also regulate neonatal inflammation, host protective immunity and myelopoiesis during polymicrobial sepsis. Neonatal (5–7 days) C57BL/6 and caspase-1/11^−/− mice underwent a low-lethality caecal slurry model of intra-abdominal sepsis (LD_25–45). Ablation of caspase-1/11, but not apoptosis-associated speck-like protein containing a CARD domain or nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), improved neonatal survival following septic challenge compared with wild-type mice (P < 0·001), with decreased concentrations of inflammatory cytokines in the serum and peritoneum. Surprisingly, caspase-1/11^−/− neonates also exhibited increased bone marrow and splenic haematopoietic stem cell expansion (P < 0·001), and increased concentrations of granulocyte and macrophage colony-stimulating factors in the peritoneum (P < 0·001) after sepsis. Ablation of caspase-1/11 signalling was also associated with increased recruitment of peritoneal macrophages and neutrophils (P < 0·001), increased phagocytosis by neutrophils (P = 0·003), and decreased bacterial colonization (P = 0·02) in the peritoneum. These findings suggest that endogenous caspase-1/11 activity, independent of the NLRP3 inflammasome, not only promotes the magnitude of the inflammatory response, but also suppresses protective immunity in the neonate, so contributing to innate immune dysfunction and poor survival in neonatal sepsis.     

Cold-Water Immersion and the Treatment of Hyperthermia: Using 38.6��C as a Safe Rectal Temperature Cooling Limit

Context:

Cold-water immersion is recommended for the immediate field treatment of exertional heat stroke. However, concerns exist over potential overcooling of hyperthermic individuals during cold-water immersion.

Objective:

To evaluate the recommendation that removing previously hyperthermic individuals from a cold-water bath at a rectal temperature (T_re) of 38.6°C would attenuate overcooling.

Design:

Controlled laboratory study.

Setting:

University research laboratory.

Patients or Other Participants:

Participants included 6 men and 4 women (age  =  22 ± 3 years, height  =  172 ± 10 cm, mass  =  67.8 ± 10.7 kg, body fat percentage  =  17.1% ± 4.5%, maximum oxygen consumption  =  59.3 ± 8.7 mL·kg⁻¹·min⁻¹).

Intervention(s):

After exercising at an ambient temperature of 40.0°C for 38.5 ± 9.4 minutes, until T_re reached 39.5°C, participants were immersed in a 2.0°C circulated water bath until T_re decreased to either 37.5°C or 38.6°C. Subsequently, participants were removed from the water bath and recovered for 20 minutes at an ambient temperature of 25°C.

Main Outcome Measure(s):

Rectal and esophageal temperatures were measured continuously during the immersion and recovery periods.

Results:

Because of the experimental design, the overall time of immersion was greater during the 37.5°C trial (16.6 ± 5.7 minutes) than the 38.6°C trial (8.8 ± 2.6 minutes) (t₉  =  −4.740, P  =  .001). During the recovery period after cold-water immersion, both rectal (F_1,9  =  50.540, P < .001) and esophageal (F_1,6  =  20.365, P  =  .007) temperatures remained greater in the 38.6°C trial than in the 37.5°C trial. This was evidenced by low points of 36.47°C ± 0.70°C and 37.19°C ± 0.71°C for rectal temperature (t₉  =  2.975, P  =  .016) and of 35.67°C ± 1.27°C and 36.72°C ± 0.95°C for esophageal temperature (t₆  =  3.963, P  =  .007) during the recovery period of the 37.5°C and 38.6°C trials, respectively.

Conclusions:

Immersion for approximately 9 minutes to a rectal temperature cooling limit of 38.6°C negated any risk associated with overcooling hyperthermic individuals when they were immersed in 2°C water.     

Alterations in immune cell subsets and their cytokine secretion profile in childhood idiopathic thrombocytopenic purpura (ITP)

Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3⁺, CD4⁺, CD8⁺) and B (CD19⁺) lymphocytes, natural killer (NK) (CD16⁺56⁺) and regulatory T (T_reg) [CD4⁺CD25^+highforkhead box protein 3 (FoxP3)⁺] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF-α)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of T_reg (P < 0·001) and natural killer (NK) (P < 0·001) cells were significantly decreased in ITP patients compared to healthy controls. A negative correlation was reported between the percentage of T_reg cells and development of acute (r = −0·737; P < 0·01) and chronic (r = −0·515; P < 0·01) disease. All evaluated cytokines (IFN-γ, TNF-α, IL-4, IL-6 and IL-10) were elevated significantly in ITP patients (P < 0·001, P < 0·05, P < 0·05, P < 0·05 and P < 0·001, respectively) compared to controls. In conclusion, our data shed some light on the fundamental role of immune cells and their related cytokines in ITP patients. The loss of tolerance in ITP may contribute to the dysfunction of T_regs. Understanding the role of T cell subsets will permit a better control of autoimmunity through manipulation of their cytokine network.     

Screening of Traditionally Used Endemic Soqotraen Plants for Cytotoxic Activity

Thirty extracts obtained from 10 endemic plant species belonging to 8 plant families used in the traditional medicine in Socotra have been tested for cytotoxic activity against FL-cells. Extracts of Eureiandra balfourii and Commiphora ornifolia showed the strongest activity against FL-cells with IC₅₀ < 10 µg/ml and 39.3 µg/ml respectively.     

A pilot study on reparixin,a CXCR1/2 antagonist,to assess safety and efficacy in attenuating ischaemia–reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery

Reparixin, a CXCR 1/2 antagonist, has been shown to mitigate ischaemia–reperfusion injury (IRI) in various organ systems in animals, but data in humans are scarce. The aim of this double-blinded, placebo-controlled pilot study was to evaluate the safety and efficacy of reparixin to suppress IRI and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG). Patients received either reparixin or placebo (n = 16 in each group) after induction of anaesthesia until 8 h after cardiopulmonary bypass (CPB). We compared markers of systemic and pulmonary inflammation, surrogates of myocardial IRI and clinical outcomes using Mann–Whitney U- and Fisher''s exact tests. Thirty- and 90-day mortality was 0% in both groups. No side effects were observed in the treatment group. Surgical revision, pleural and pericardial effusion, infection and atrial fibrillation rates were not different between groups. Reparixin significantly reduced the proportion of neutrophil granulocytes in blood at the beginning [49%, interquartile range (IQR) = 45–57 versus 58%, IQR = 53–66, P = 0·035], end (71%, IQR = 67–76 versus 79%, IQR = 71–83, P = 0·023) and 1 h after CPB (73%, IQR = 71–75 versus 77%, IQR = 72–80, P = 0·035). Reparixin patients required a lesser positive fluid balance during surgery (2575 ml, IQR = 2027–3080 versus 3200 ml, IQR = 2928–3778, P = 0·029) and during ICU stay (2603 ml, IQR = 1023–4288 versus 4200 ml, IQR = 2313–8160, P = 0·021). Numerically, more control patients required noradrenaline ≥ 0·11 μg/kg/min (50 versus 19%, P = 0·063) and dobutamine (50 versus 25%, P = 0·14). Therefore, administration of reparixin in CABG patients appears to be feasible and safe. It concurrently attenuated postoperative granulocytosis in peripheral blood.     

Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

Several studies correlated genetic background and pancreatic islet-cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and β cell function. This characterization has a potential importance with regard to T1AD patients'' stratification and follow-up in therapeutic prevention. In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1β, tumour necrosis factor (TNF)-α, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0·80; P = 0·000), IL-8 and TNF-α (r = 0·60; P = 0·000); IL-8 and IL-12 (r = 0·57; P = 0·001) and TNF-α and IL-12 (r = 0·93; P = 0·000). Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = −0·45; P = 0·011) and CCL2 (r = −0·65; P = 0·000), while IA-2A showed a negative correlation with IL-10 (r = −0·38; P = 0·027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. In summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA-2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre-T1AD phase could help to explain the mechanistic of the well-known role of IA-2A as a more specific marker of beta-cell damage than GADA during the natural history of T1AD.     

Two different fatigue protocols and lower extremity motion patterns during a stop-jump task

Context:

Altered neuromuscular control strategies during fatigue probably contribute to the increased incidence of non-contact anterior cruciate ligament injuries in female athletes.

Objective:

To determine biomechanical differences between 2 fatigue protocols (slow linear oxidative fatigue protocol [SLO-FP] and functional agility short-term fatigue protocol [FAST-FP]) when performing a running-stop-jump task.

Design:

Controlled laboratory study.

Setting:

Laboratory.

Patients or Other Participants:

A convenience sample of 15 female soccer players (age = 19.2 ±0.8 years, height = 1.67±0.05m, mass = 61.7 + 8.1 kg) without injury participated.

Intervention(s):

Five successful trials of a running–stop-jump task were obtained prefatigue and postfatigue during the 2 protocols. For the SLO-FP, a peak oxygen consumption (V˙o₂peak) test was conducted before the fatigue protocol. Five minutes after the conclusion of the V˙o₂peak test, participants started the fatigue protocol by performing a 30-minute interval run. The FAST-FP consisted of 4 sets of a functional circuit. Repeated 2 (fatigue protocol) × 2 (time) analyses of variance were conducted to assess differences between the 2 protocols and time (prefatigue, postfatigue).

Main Outcome Measure(s):

Kinematic and kinetic measures of the hip and knee were obtained at different times while participants performed both protocols during prefatigue and postfatigue.

Results:

Internal adduction moment at initial contact (IC) was greater during FAST-FP (0.064 ±0.09 Nm/kgm) than SLO-FP (0.024±0.06 Nm/kgm) (F_1,14 = 5.610, P=.03). At IC, participants had less hip flexion postfatigue (44.7°±8.1°) than prefatigue (50.1°±9.5°) (F_1,14 = 16.229, P=.001). At peak vertical ground reaction force, participants had less hip flexion postfatigue (44.7°±8.4°) than prefatigue (50.4°±10.3°) (F_1,14 = 17.026, P=.001). At peak vertical ground reaction force, participants had less knee flexion postfatigue (−35.9°±6.5°) than prefatigue (−38.8°±5.03°) (F_1,14 = 11.537, P=.001).

Conclusions:

Our results demonstrated a more erect landing posture due to a decrease in hip and knee flexion angles in the postfatigue condition. The changes were similar between protocols; however, the FAST-FP was a clinically applicable 5-minute protocol, whereas the SLO-FP lasted approximately 45 minutes.     

Antibacterial agents from the leaves of Crinum purpurascens herb (Amaryllidaceae)

Background

Typhoid fevers and urogenital infections continue to be serious health problems in developing countries. In our search for therapeutic agents from natural sources with potential for the treatment of typhoid fevers and urogenital infections, extract and compounds were obtained from Crinum purpurascens and tested.

Methods

Two alkaloids (4,5-ethano-9,10-methylenedioxy-7-phenanthridone or hippadine (1) and 4,5-ethano-9-hydroxy-10-methoxy-7-phenanthridone or pratorimine (2)) and one steroid (â-D-glucopyranoside of sitosterol (3)) were isolated from the CH₂Cl₂/MeOH (1:1) leaf extract of Crinum purpurascens and screened for antibacterial activity using both agar diffusion and broth dilution techniques.

Results

For the CH₂Cl₂/MeOH extract, the MIC values obtained were 3 mg/ml (against P. aeruginosa), 4 mg/ml (against E. coli, K. pneumoniae and S. aureus) and 6 mg/ml (against S. typhi and S. paratyphi B), whereas the MBC values varied between 7 and 12 mg/ml. For compound 1, the MIC values varied between 200 and 250 µg/ml, whereas the MBC value was 300 µg/ml against all the bacteria strains used. Compound 2 did not show any antimicrobial activity against these bacteria strains. For compound 3, the MIC values varied between 250 and 300 µg/ml, whereas the MBC values were 300 µg/ml (against S. typhi and S. paratyphi B) and > 300 µg/ml (against the other bacteria strains).

Conclusion

These data suggest that C. purpurascens leaf extract contains antibacterial agents which could be used in the treatment of typhoid fevers and urogenital infections.     

Biological Activities of Asparagus Racemosus

Cytotoxic, antioxidant, tyrosinase inhibitory, antimicrobial activities of the crude ethanol extract of dry powdered roots of Asparagus racemosus (Liliaceae) were investigated. The LC₅₀ to brine shrimp was 2189.49 µg/ml; the EC₅₀ for DPPH radical scavenging was 381.91 µg/ml; the IC₅₀ for tyrosinase inhibition was 7.98 mg/ml. The extract was active at 5–20 mg/ml against various pathogenic microbial (16 species, 18 strains) using the agar dilution assay, with the minimum inhibitory concentration (MIC) between 10–20 mg/ml for enteropathogens, the MIC between 5–20 mg/ml for dermatopathogens, and MIC = 10 mg/ml for a pneumonia causing bacteria Klebsiella pneumoniae. TLC and HPLC finger printing showed the presence of steroids-terpenes, alkaloids and flavonoids.     

The augmented neutrophil respiratory burst in response to Escherichia coli is reduced in liver cirrhosis during infection

Several functional abnormalities in phagocytes from patients with liver cirrhosis contribute to an increased risk of infection. An increased resting respiratory burst has been observed in neutrophils from cirrhotic patients. We investigated whether an infection in cirrhosis affects the respiratory burst capacity of neutrophils and monocytes in response to Escherichia coli. This study included 45 hospitalized patients with liver cirrhosis and clinical signs of infection, 39 patients with liver cirrhosis in the absence of infection and 29 healthy subjects. Respiratory burst, lipopolysaccharide-binding protein (LBP), and immunoglobulin (Ig)G-autoantibodies against oxidized low-density lipoproteins (ab-oxLDL) were measured. The fraction of neutrophils spontaneously producing reactive oxygen species (ROS) was elevated in liver cirrhosis (P < 0·01). The neutrophil resting burst increased with Child–Pugh stage (P = 0·02) and correlated with augmented ROS release in response to opsonized E. coli (P < 0·05). Although LBP was increased in patients with cirrhosis (P < 0·01), higher LBP levels correlated with a lower resting burst in neutrophils (r_s = –0·395; P < 0·01). In the presence of infection, the resting burst was unaltered. However, neutrophil ROS release in response to E. coli was reduced markedly (P = 0·01), and it decreased as serum C-reactive protein (CRP) concentration rose (r_s = −0·437; P < 0·01), indicating the development of a sepsis-like immune paralysis. A positive correlation between ab-oxLDL and ROS release was observed (P < 0·01). In conclusion, the respiratory burst increases with severity of liver cirrhosis but is restrained by increasing LBP levels. Augmented ROS release in response to E. coli is accompanied by elevated markers of oxidative damage and becomes exhausted in the presence of infection.     

Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus

INTRODUCTION:

Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy.

METHODS:

We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation).

RESULTS:

Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P =  0.257), HbA_1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P = 0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5%) vs. the Ins group (54.0% ± 16.3%; P = 0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3%) and Ins groups (111.9% ± 28.5%; P = 0.888).

CONCLUSIONS:

Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.