Military field training exercise with prolonged physical activity and sleep restriction causes hormonal imbalance in firefighter cadets.

PURPOSE: To evaluate the impact of the "Search and rescue" field military training exercise (SR_FTX) on hormonal modulation and identify their possible correlation with physical and cognitive performance. METHODS: An observational (before and after) study was carried out, with male firefighters cadets (n = 42; age = 23[22;27] years) undergoing a nine-day military exercise (SR_FTX). The Countermovement jump (physical performance), the Stroop test (cognitive alertness), and blood tests for testosterone, cortisol, GH, and IGF-1 were applied. Wilcoxon for paired samples and Spearman's correlation tests were used. RESULTS: Testosterone (751.10 [559.10;882.8] vs. 108.40 [80.12;156.40] ng/dL) and IGF-1 (217.5 [180;239.30] vs. 105 [93;129] ng/mL) significantly decreased while GH (0.10 [0.06;0.18] vs. 1.10 [0.58;2.28] ng/mL) and cortisol (9.60 [8.20;11.55] vs. 15.55 [12.28;18.98] ug/dL) significantly increased. Physical performance (31.2 [30.04;35.4] vs. 21.49 [19,02;23,59] cm) and cognitive alertness were significantly worse after SR_FTX (Congruent task: 1,78 (0183) vs. 1,56 (0185) response/s and incongruous task: 1,23 (0191) vs. 1,02 (0207) response/s). The physical performance showed a strong correlation with testosterone (rho = 0.694) and regular correlations with both IGF-1 (rho = 0.598) and cortisol (rho = - 0.580). The Stroop test presented weak correlations with GH (rho = - 0.350) and cortisol (rho = - 0.361). CONCLUSION: SR_FTX negatively impacted hormonal modulation, physical and cognitive performance. These findings could help commanders decide to replace the employed firefighters in a real mission more frequently. Also, if the real scenario allows, they could think about providing better work conditions, such as improving caloric intake and rest periods, to preserve the military performance and health.

Free thyroxine concentrations by equilibrium dialysis and chemiluminescent immunoassays in 13 hypothyroid dogs positive for thyroglobulin antibody.

OBJECTIVE: To determine if concentrations of free thyroxine (FT4) measured by semi-automated chemiluminescent immunoassay (CLIA) correspond to FT4 determined by equilibrium dialysis (ED) in hypothyroid dogs positive for thyroglobulin antibody (TGA). ANIMALS: Thirteen TGA-positive dogs classified as hypothyroid based on subnormal FT4 concentrations by ED. METHODS: Qualitative assessment of canine TGA was performed using an enzyme-linked immunosorbent assay. Serum total thyroxine and total triiodothyronine concentrations were measured by radioimmunoassay. Serum FT4 concentration was determined by ED, and also by semi-automated CLIA for human FT4 (FT4h) and veterinary FT4 (FT4v). Canine thyroid stimulating hormone concentration was measured by semi-automated CLIA. RESULTS: Each dog's comprehensive thyroid profile supported a diagnosis of hypothyroidism. For detection of hypothyroidism, sensitivities of CLIA for FT4h and FT4v were 62% (95% CI, 32-85%) and 75% (95% CI, 36-96%), respectively, compared to FT4 by ED. Five of 13 (38%) dogs had FT4h and 2 of 8 (25%) dogs had FT4v concentrations by CLIA that were increased or within the reference range. Percentage of false-negative test results for FT4 by CLIA compared to ED was significantly (P < .0001 for FT4h and P < .001for FT4v) higher than the hypothesized false-negative rate of 0%. CONCLUSIONS AND CLINICAL IMPORTANCE: Caution should be exercised in screening dogs for hypothyroidism using FT4 measured by CLIA alone. Some (25-38%) TGA-positive hypothyroid dogs had FT4 concentrations determined by CLIA that did not support a diagnosis of hypothyroidism.

Exercise improves the Th1 response by modulating cytokine and NO production in BALB/c mice.

Physical exercise can improve health and may lead to changes in the functionality of the immune system. Moderate intensity exercise can reduce the risk of infection by shifting the overall immune response towards a T helper type 1 pattern. This study investigates the effect of 12 weeks of swimming on the cytokine profile of lymph node cells and macrophages and of the nitric oxide production by these cells. BALB/c mice were divided into 2 groups. The exercise group was subjected to swimming exercise. Lymph node cells culture showed that concentrations of interferon-γ and tumour necrosis factor-α were higher in the exercised group, while levels of interleukine-4 and interleukine-10 were significantly decreased in this group. The interleukine-10/interferon-γ ratio tended towards a T helper type 1 profile. Moreover, macrophages isolated from exercised mice produced more interleukine-12 and tumour necrosis factor-α following lipopolysaccharide stimulus. Challenging these macrophages with Leishmania major resulted in higher interleukine-12 production than was observed with macrophages from the control group. Nitric oxide production was increased in macrophages isolated from exercised group following lipopolysaccharide stimulus but not following infection with Leishmania major. These data suggest that exercise biases the immune system towards a T helper type 1 response profile.

Maximum acute exercise tolerance in hyperthyroid and hypothyroid rats subjected to forced swimming.

Thyroid dysfunction can compromise physical capacity. Here, we analyze the effects of hyperthyroidism and hypothyroidism on maximum swim time in rats subjected to acute forced swimming, as an indicator of anaerobic capacity. Animals were forced to swim against a load (5% of body weight) attached to the tail and were killed 48 hours after the last test. Hyperthyroid rats were treated with thyroxine (50 mug/100 g body weight, i. p. for 7 days). The hypothyroid group received 0.03% methimazole in the drinking water for 4 weeks. Thyroid state was confirmed by alterations in serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and liver mitochondrial glycerol phosphate dehydrogenase (mGPD) activity. Hyperthyroid rats presented significantly lower visceral fat mass (VFM) and higher food intake (p<0.05) with unchanged body weight. Maximum swim time (MST), glycogen content (skeletal muscle and liver), and leptin levels were lower while corticosterone was higher (p<0.05). In hypothyroid rats body weight was lower (p<0.05), without changes in VFM. Tested at 7-day intervals, MST was lower for tests 2, 3, and 4 (p<0.05). Muscle glycogen was higher in extensor digitorum longus (EDL) and soleus (p<0.05), without changes in liver. Serum corticosterone was lower, while leptin was higher (p<0.05). These results suggest that in hyperthyroid and hypothyroid rats, thyroid hormones together with corticosterone and/or leptin may impair exercise capacity differently through its known effects on glycogen metabolism.

Probing actomyosin interactions with 2,4-dinitrophenol.

Access to different intermediates that follow ATP cleavage in the catalytic cycle of skeletal muscle actomyosin is a major goal of studies that aim toward an understanding of chemomechanical coupling in muscle contraction. 2,4-Dinitrophenol (DNP, 10(-2) M) inhibits muscle contraction, even though it accelerates the ATPase activity of isolated myosin. Here we used myosin subfragment 1 (S1), acto-S1 and mammalian skinned fibers to investigate the action of DNP in the presence of actin. DNP increases acto-S1 affinity and at the same time reduces the maximum rate of turnover as [actin]-->infinity. In skinned fibers, isometric force is reduced to the same extent (K0.5 approximately equal to 6 mM). Although actin activates Pi release from S1 at all DNP concentrations tested, the combination of enhanced S1 activity and reduced acto-S1 activity leads to a reduction in the ratio of these two rates by a factor of 30 at the highest DNP concentration tested. This effect is seen at low as well as at high actin concentrations and is less pronounced with the analog meta-nitrophenol (MNP), which does not inhibit the acto-S1 ATPase. Arrhenius plots for acto-S1 are parallel and linear between 5 and 30 degrees C, indicating no abrupt shifts in rate-limiting step with either DNP or MNP. Analysis of the reduction in isometric force with increasing Pi concentrations suggests that DNP and MNP stabilize weakly bound cross-bridges (AM.ADP.Pi). In addition, MNP (10(-2) M) increases the apparent affinity for Pi.

Specificity and kinetic effects of nitrophenol analogues that activate myosin subfragment 1.

2,4-Dinitrophenol (DNP) activates the myosin ATPase of mammalian skeletal muscle in the presence of Ca2+ or Mg2+, and inhibits it when the bivalent cations are replaced by K+ and EDTA. Activation of Mg2+ATPase is abolished by the presence of unregulated actin. 3-Nitrophenol (3-NP) is also an activator, whereas other analogues (2-nitrophenol, 2-NP, and 4-nitrophenol, 4-NP) are much less effective. Concentrations required for their half-maximal effects (K0.5) range from 2 to 15 mM for 3-NP and DNP in the presence of different cations, and the sequence for the analogues is 3-NP<=DNP<<2-NP approximately 4-NP, which is apparently unrelated to either hydrophobicity or pK. DNP and 3-NP have almost identical effects on the ATPase activity of chymotryptic subfragment 1 as they do on myosin, which is an indication that their target is the globular head region rather than the tail, or the 18 kDa (regulatory) light chain. Analysis of the ATP concentration dependence for subfragment- 1 ATPase in the presence of Ca2+ or Mg2+ shows that DNP activates only at high substrate concentrations, becoming increasingly effective with ATP concentrations in the physiological range. At low substrate concentrations, DNP inhibits hydrolysis by increasing the apparent Km for ATP at the catalytic site. In the presence of Mg2+, it mimics the effect of actin, which increases the Km and accelerates the release of products following hydrolysis. At high substrate concentrations, activation by DNP appears to involve a kinetic component with low affinity for ATP that can increase the overall reaction rate by a factor of 2- to 9-fold, depending on the bivalent cation. This low-affinity component is either induced by the drug (in the presence of Mg2+) or shifted by the drug to a lower ATP concentration range (in the presence of Ca2+).

Prevalence of hyperactive digastric muscles during swallowing as measured by electromyography in patients with myofascial pain dysfunction syndrome.

One purpose of this clinical study is to establish a relationship between the hyper activity of the digastric muscles and predisposition of an individual to MPDS (myofacial pain dysfunction syndrome). If a population predisposed to MPD could be identified by an early diagnosis, intervention and treatment could eliminate potential pain in adulthood. Secondly, can the employment of electromyography to aid in the diagnosis of patients with MPD be helpful in establishing a program of prevention and treatment? Thirty-one patients, male and female, were randomly selected from among those routinely diagnosed as having myofascial pain dysfunction syndrome by the dental staff at the Long Island Center for Craniofacial Pain. Eighteen patients who did not experience any symptoms of facial pain comprised the control group in the study. This study demonstrated that the average trace readings which indicate the activity of the digastric muscles, as measured by the electromyogram from patients experiencing facial pain were significantly higher than those from patients without pain symptoms. In every instance, the correlation between facial pain and abnormal swallow patterns which are a cause of hyperactivity of the digastrics was confirmed.

[The motility of the biliary tract studied with 99mTc-Br-IDA in patients with type-2 diabetes mellitus]. / Studio sulla motilità delle vie biliari con 99mTc-Br-IDA in pazienti con diabete mellito di tipo II.

Autonomic neuropathy in diabetes mellitus can cause alterations of the motor function of various segments of the gastroenteric apparatus. With hepatocholangio-cholecystiscintigraphy-HIDA we have studied the motility of the biliary system in patients with diabetes mellitus type II. The research has been carried out in 29 patients with diabetic autonomic neuropathy; 12 healthy volunteers have been studied to compare the results obtained. The results showed a delay in the appearance of radionucleotide in the small intestine of diabetic subjects compared to controls with statistical significance. Moreover the diabetic subjects with a serious neuropathic injury showed increased intestinal transit time. These results match those obtained by other authors that have studied the cholecystic emptying in diabetic subjects with other methods. Consequently the biliary system is also affected by the diabetic autonomic neuropathy that can be in its turn the cause of other pathologies such as biliary lithiasis.

Conservative treatment for T2-T4 bladder cancer with primary chemotherapy and radiotherapy: a pilot study.

AIMS AND BACKGROUND: After radical cystectomy, with or without pelvic radiotherapy, more than 50% of patients affected by infiltrating bladder cancer died of distant metastases. Polychemotherapy yields 25% complete remissions (CR) in patients with invasive transitional cell bladder carcinoma; although many concerns exist about the duration of such CR. This study was undertaken with the aim of evaluating the efficacy and safety of an integrated chemo-radiotherapeutic treatment, in order to broaden indications to a conservative surgical therapy. METHODS: Thirty-three consecutive patients with bladder urothelial cancer T2-T4, N0, M0, have been treated. Patients received neoadjuvant chemotherapy (rescue-M-VEC) consisted of methotrexate 30 mg/sqm plus folinic acid 15 mg after 24 h on days 1, 15, 22; vinblastine 3 mg/sqm on days 1, 15 and 22; epidoxorubicin 30 mg/sqm on day 1; cisplatin 70 mg/sqm on day 1. This cycle was repeated on day 29. After 2 cycles of rescue-M-VEC, patients underwent pelvic cobalt teletherapy 40 Gy combined with low dose cisplatin 25 mg/sqm/week. After restaging, responding patients underwent further radiation therapy (24 Gy) as booster consolidation. RESULTS: After 2 cycles of chemotherapy and pelvic radiotherapy 14/31 evaluable patients (45.2%) achieved CR and 11/31 (35.4%) partial remission, with an overall response rate of 80.6% (25/31). With a median follow up of 21 months the actuarial survival rate at 24 months was equal to 79.8%. Eleven radical cystectomies were performed, 6 of which at restaging in non responding patients and 5 during the follow up due to relapse. Of the 25 patients selected for bladder conservation, 12 (48%) have not yet shown relapses. Three out of 31 (9.7%) patients died of distant metastases. No severe toxicity has been observed: moreover no patient developed stomatitis after chemotherapy. CONCLUSIONS: Our results seem encouraging but longer follow-up and further phase III studies need to be carried out to demonstrate the feasibility of conservative treatment in muscle infiltrating bladder cancer.

Activation of factor XI in plasma is dependent on factor XII.

The activation of factor XI initiates the intrinsic coagulation pathway. Until recently it was believed that the main activator of factor XI is factor XIIa in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface. Two recent reports have presented evidence that in a purified system factor XI is activatable by thrombin together with the soluble polyanion dextran sulfate. To assess the physiological relevance of these findings we studied the activation of factor XI in normal and factor XII-deficient plasma. We used either kaolin/cephalin or dextran sulfate as a surface for the intrinsic coagulation pathway, tissue factor to generate thrombin via the extrinsic pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is rapidly cleaved on incubation with kaolin. The kinetics appear to be exponential with half the maximum cleavage at 5 minutes. Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. Tissue factor (1:500) added to plasma did not induce cleavage of factor XI during a 90-minute incubation, although fibrin formation within 30 seconds indicated that thrombin was generated via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to 50% prothrombin activation) directly to factor XII deficient or normal plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to instantaneous fibrinogen cleavage, but again no cleavage of factor XI was observable. We conclude that in plasma surroundings factor XI is not activated by thrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable.

[Effects of fenoverine on biliary kinetics evaluated by hepatobiliary scintigraphy with 99mTc-Br-IDA]. / Effetti della fenoverina sulla cinetica biliare valutata con scintigrafia epatobiliare con 99mTc-Br-IDA.

Hepatobiliary scintigraphy was used to evaluate the action of fenoverine in 16 patients suffering from dyskinesia of the biliary tract; the drug was administered in doses of 300 mg per day per os for 20 days, the patients being subjected to hepatobiliary scintigraphy before and after treatment. The following parameters--accurate indicators of the motor coordination of the biliary tract--were evaluated: tracer appearance time in the gallbladder (Tc) and in the intestine (Ti). After treatment there was a normalization of these two parameters which initially were extended. Statistical analysis showed a highly significant reduction in these times. Stress is laid on the importance of hepatobiliary scintigraphy in the diagnosis of biliary dyskinesia and on the effectiveness of fenoverine in the treatment of this conditions.

[Br-IDA in the evaluation of papillo-sphincterotomy and choledochoduodenostomy]. / La Br-IDA nella valutazione della papillosfinterostomia e della coledocoduodenostomia.

Twenty-three patients who had undergone surgery for non-neoplastic pathologies of the terminal choledochus were studied using 99mTc Br-IDA. This method is used to study patients operated for PST of CDS because: 1) is not invasive and does not cause allergies; 2) it allows a physiological evaluation of biliary flow to be obtained; 3) it is not influenced by the patient's body structure, by the presence of intestinal gas or costo-chondral calcification; 4) the radiation dose absorbed by the patient is very low; 5) it does not require any special preparation of the patient. Papillosphincterotomy was performed in 16 patients and choledochoduodenostomy in 7 patients. Follow-up varied between a minimum of two and maximum of eight years. The morphology of the biliary tract remained normal in all cases or was only slightly dilated. Captation and excretion time remained within normal values. Marker activity in the duodenum appeared early in all cases. A duodenogastric reflux was only observed in one patient among those undergoing PST, whereas it was observed almost constantly following CDS.

Mitoxantrone (M) and vinblastine (V) in the treatment of advanced breast cancer.

Twenty-four patients with metastatic breast cancer, all but 1 pretreated with one or more chemotherapeutic regimens, were entered in a pilot study to assess toxicity and efficacy of the combination mitoxantrone and vinblastine. Dominant sites of metastases were viscera in 9 patients, bone in 10 and soft tissues in 5. All patients received mitoxantrone 10 mg/m2 i.v. on day 1 and vinblastine 1.7 mg/m2 by 4 hour infusion on days 3, 4 and 5, every 3-4 weeks. Objective responses (1 CR, 7 PR) were observed in 8 (38%) of the 21 evaluable patients. Median duration of response was 10.5 months. Of 12 patients pretreated with an anthracycline containing regimen, 4 responded (1 CR and 3 PR). Major toxicity was myelosuppression, grade 4 in 2 cases and grade 3 in 2 others. No evident alopecia was observed and only 1 case of grade 1 cardiac toxicity. In conclusion, mitoxantrone followed by vinblastine is an effective regimen in metastatic breast cancer also in pretreated patients, and previous anthracycline administration does not seem to reduce the percentage of response. Moreover, toxicity is generally mild.