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Coronary artery-pulmonary artery fistula originating from three major coronary branches associated with exertional chest pain and tachycardia-dependent left bundle branch block.

A 49-year-old male was admitted to our hospital because of chest pain. The pain occurred simultaneously with tachycardia-dependent left bundle branch block (LBBB) during exercise-stress and atropine-stress electrocardiogram (ECG) and on 24-h ambulatory ECG monitoring. Myocardial perfusion and metabolic scintigraphy with Tl-201 and I-123 BMIPP, respectively, showed no evidence of ischemia. Coronary arteriography revealed no atherosclerotic lesions, but did show a fistula between three major coronary arteries and the main pulmonary artery. The left-to-right shunt was undetectably small. Administration of diltiazem and metoprolol suppressed LBBB by attenuating the heart rate response to exercise, and reduced the chest pain. Therefore we presume that the exertional chest pain was not caused by myocardial ischemia but by the tachycardia-dependent LBBB. Coronary artery-pulmonary artery fistula is the most common type of coronary artery fistulae found incidentally in adulthood. Involvement of three major coronary branches is, however, rare. The case is discussed with a review of the literature.

Bundle-Branch Block↗

Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure.

Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.

Acetates↗

Long-term treatment with subantimicrobial dose doxycycline exerts no antibacterial effect on the subgingival microflora associated with adult periodontitis.

BACKGROUND: The purpose of this study was to determine whether treatment with subantimicrobial dose doxycycline (SDD), 20 mg bid, exerted an antimicrobial effect on the microflora associated with adult periodontitis. METHODS: Following the approval of the protocol and informed consent forms by the respective IRBs at the University of Florida and West Virginia University, 76 subjects with adult periodontitis were entered and randomly assigned to receive SDD or placebo. A split-mouth design was utilized, with each subject receiving subgingival scaling and root planing (SRP) in two quadrants immediately following baseline data collection, while the remaining two quadrants were left unscaled (non-SRP). Microbial samples were collected prior to treatment, after 3, 6, and 9 months of treatment, and after 3 months of no treatment. The samples were examined by microscopy and by enumeration on selective and non-selective media. RESULTS: All treatments resulted in statistically significant decreases in the proportions of spirochetes and motile rods (P <0.05) and in an increase in the proportion of coccoid forms (P <0.0001) relative to baseline. No between-treatment differences were detected between the SDD and placebo treatments in either the SRP or non-SRP design, with the exception of the small and large spirochetal groups. The spirochetal proportions present in the SDD group were significantly lower (P<0.05) than the paired placebo group during the 9-month treatment and was preceded by a significant decrease (P<0.01) in the proportion of microbiologic sample sites that bled on probing. No between- treatment differences were detected in any of the other microbial parameters. CONCLUSION: The microbial differences observed were attributed to the anticollagenase and anti-inflammatory properties of SDD and not to an antimicrobial effect.

Adult↗

Weifuchun ( ) exerts therapeutic effects on gastric fundic gland polyps by promoting ferroptosis.

OBJECTIVE: To investigate the therapeutic effects of Chinese medicine Weifuchun (WFC, ) on gastric fundic gland polyps (FGPs). METHODS: FGPs organoids were constructed with patients-derived samples. The morphology and size of FGPs organoids were detected using bright-field imaging. Effective components and corresponding potential targets of WFC were screened using multiple open-source databases and research on Traditional Chinese Medicine or compound formulas. Core genes were identified through protein-protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the core genes were conducted. The interactions between main components and core targets were analyzed through the FerrDb database. The expressions of core targets were detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: After WFC treatment, the number and size of FGPs organoids were significantly reduced. Twenty nine active drug components and 162 candidate targets of WFC for treating FGPs were identified, including 37 targets related to ferroptosis. Quercetin, Glaucocalyxin B, Melissoidesin U, Melissoidesin O, Hesperetin, Glaucocalyxin A, Angustifolin, Melissoidesin M, Di-n-octyl phthalate, and beta-sitosterol were identified as the main active compounds. SRC proto-oncogene, non-receptor tyrosine kinase, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, phosphoinositide-3-kinase regulatory subunit 1, and AKT serine/threonine kinase 1 were identified as the primary targets. KEGG pathways related to carcinogenesis, cell proliferation and metabolism, and oxidative stress. WFC promoted FGPs organoids' death and could be reversed by ferroptosis inhibitor of Erastin. The qRT-PCR results showed that WFC treatment could regulate the mRNA expression levels of solute carrier family 7 member 11, acyl-CoA synthetase long chain family member 4, and arachidonate 15-lipoxygenase, type B. CONCLUSION: WFC may exert its therapeutic effects by inducing ferroptosis in FGPs cells.

Humans↗

[The effect of the motion of forefoot joint at the force exerted upon the floor during walking exercise].

In walking exercise the human body is exposed to external forces. Some of them are produced by constraints such as surface, shoes or opponent. In kick action of walking, the ground reaction force (GRF) is the most important external force. The magnitude of the GRF, its direction, and point of application have an influence on the load on the human body. The purpose of this study is to clarify the role of forefoot joint (artt. metatarsophalangeae) at the force exerted upon the floor during kick action of walking. The device used in this study to analyze the GRF and its three components consists of Kistler's force platform. Output from force transducer was collected online with a TEAC data recorder and MEM-4101 minicomputer. The impact force measurements were taken from the anterior-posterior force time curves at the take-off for 1 subject walking 10 trials at 2 m/sec with 2 different pairs of shoes (Shoes 1: thin sole of 4mm, and Shoes 2: thick sole of 40mm) and without shoes. High speed (200f/sec) cinematography was also used to analyze the angular displacement of forefoot joint at the take-off of walking exercise. The force acting at the forefoot joint may produce the anterior-posterior force of the GRF which is defined as the propelling power acting on the human body during walking exercise. The result showed that the impact force peak occurred 40-60 msec before take-off and the propelling part of kick action accounted for only about 6% of the external force.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise↗

Examination of the reproducibility of grip force and muscle oxygenation kinetics on maximal repeated rhythmic grip exertion.

The contribution of physiological mechanisms involving force-exertion value during maximal repeated rhythmic muscle contraction work changes over time. The purpose of this study was to examine the reproducibility of grip force and muscle oxygenation kinetics with a decrease of the gripping force during maximal repeated rhythmic grip (RRG). Subjects were 10 males, aged 20-26 years (height 173.9+/-7.3 cm, body weight 71.5+/-11.2 kg). Each subject performed maximal repeated rhythmic grip as a target value with a target frequency of 30 grips.min(-1) for 6 min. The trial-to-trial reproducibility of Oxygenated haemoglobin (Oxy-Hb), Deoxygenated haemoglobin (Deoxy-Hb), Total haemoglobin (Total Hb) and grip force during the RRG (6 min) was very high (r(xy)=0.919-0.966) and the decreasing pattern of the force-time curve was consistent. The cross correlation coefficients of the grip force (r(xy)=0.985) and muscle oxygenation kinetics (Total Hb: 0.996, Oxy-Hb: 0.992, Deoxy-Hb: 0.995) in the pre-inflection phase (marked force decreasing phase) were very high, while these coefficients in the post-inflection phase (almost steady state phase) were low as compared with those in the pre-inflection phase. The trial-to-trial reliabilities of any parameter regarding grip were fair or high (ICC=0.686-0.927). The changing points of muscle oxygenation kinetics appeared before reaching an almost steady state, which showed a high reliability and they were considered to reflect the shift of physiological mechanisms. In particular, the intraclass correlation coefficients (ICC) for the time to reach maximum Deoxy-Hb and Oxy-Hb values and regression coefficient in an increasing phase of Oxy-Hb were very high (ICC=0.894-0.947). It was found that the trial-to-trial reproducibility of grip force and muscle oxygenation kinetics is very high during the whole 6 min in RRG, but is poor during the post-inflection phase. The reproducibility of the grip force and muscle oxygenation kinetics in the phase before reaching an almost steady state during RRG is fair, and the decrease of the grip force in this phase may be influenced by the muscle oxygenation kinetics.

Adult↗

Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa.

Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The inflammatory reactions within the male genital tract are inevitably connected with oxidative stress. Growing evidence indicates that imbalance between prooxidative and anti-oxidative substances in semen leads to metabolic and functional disorders of male germ cells and may be a primary cause of some types of infertility. The infectious factor and local tissue damage can lead to the infiltration of leukocytes to the inflammatory site. This is in an obvious way connected to the production and release of large amounts of reactive oxygen species (ROS), which trigger immune responses directed against the infectious agent, and the simultaneous secretion of numerous biological substances, thereby escalating the inflammation. Some of these factors are proteases and proinflammatory cytokines. Extended exposure of spermatozoa to ROS may lead to the peroxidation of sperm membrane lipids. Many studies point to the combined activities of inflammatory mediators in exerting toxic effects on spermatozoa. The local influences of biologically active substances released by activated leukocytes in the course of the inflammatory response and the mutual interactions of various factors (bacteria, leukocytes, proinflammatory cytokines) at the site represent a complex puzzle.

Bacterial Infections↗

[Acute leg compartment syndrome after exertion].

A case of a 22-year old soldier, with a history of pain in the leg during heavy exercise, which desisted at rest, was presented. One day before admission, the patient had felt an extreme exertion-induced pain in his right leg which had not lessenned at rest. At the same time, the patient noticed persistent severe leg edema. On physical examination, the intracompartmental pressure was 62 mmHg (> 30 mmHg). The patient was urgently operated on, and fasciotomy according to Mubarak was used. At second surgery, the debridement of the muscles of the posterior group of the leg, and the evacuation of hemathoma from the anterior and lateral group of the right leg muscles were perfomed. Postoperative recovery was uneventful. Fasciotomy wounds were closed within 14 days of the surgery. The complete physical treatment was done. Follow-up examinations 1, 3, and 6 months afterwards were satisfactory. The soldier completed his compulsory military service without any sequelae. Laboratory results were normal. Overlooked, unrecognized or surgically untreated compartment syndrome can cause severe damage, including even the loss of the extremity.

Acute Disease↗

Human pancreatic duct cells exert tissue factor-dependent procoagulant activity: relevance to islet transplantation.

Activation of the coagulation cascade contributes to early graft loss and intraportal thrombotic events in clinical islet transplantation. Although these complications were shown to be related to the presence of tissue factor in human islet preparations, the contribution of duct cells, which represent a major contaminant of clinical islet isolates, has not been specified so far. Herein, we used flow cytometry, immunohistochemistry, RT-PCR, and functional coagulation assays to demonstrate that duct cells exert a potent factor VII-dependent procoagulant activity related to their expression of tissue factor. Both the classical membrane-bound and the recently described soluble form of tissue factor were shown to be synthesized by duct cells. We conclude that contaminating duct cells contribute to early beta-cell damage after islet transplantation through their involvement in tissue factor-mediated thrombotic and inflammatory events.

Blood Coagulation Tests↗

Effect of ration and exercise on plasma creatine kinase activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine the effects of 3 rations (low grain, fat, high grain) on plasma creatine kinase (CK) activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 5 Thoroughbreds with RER and 3 healthy Thoroughbreds (control horses). PROCEDURES: Rations were formulated to meet (low-grain and fat rations) or exceed (high-grain ration) daily energy requirements. Each ration was fed to horses in a crossover design for 3 weeks. Horses were exercised on a treadmill Monday through Friday; maximum speed on Monday and Friday was 11 m/s (6% slope), on Tuesday and Thursday was 9 m/s, and on Wednesday was 4.5 m/s. Plasma CK activity and lactate concentration were determined before and after exercise. RESULTS: Horses with RER fed the high-grain ration had significantly greater CK activity and change in CK activity 4 hours after exercise, compared with those fed the low-grain ration. Horses with RER exercised at the trot or canter had significantly greater increases in CK activity, compared with those exercised at the gallop. Plasma lactate concentrations after exercise were similar in control and affected horses. Lactate concentration and CK activity were not correlated in horses with RER. CONCLUSIONS AND CLINICAL RELEVANCE: Rations high in grain and formulated to exceed daily energy requirements may increase episodes of rhabdomyolysis in thoroughbred horses susceptible to RER.

Animal Feed↗

Plasma and urine electrolyte and mineral concentrations in Thoroughbred horses with recurrent exertional rhabdomyolysis after consumption of diets varying in cation-anion balance.

OBJECTIVE: To determine whether plasma, urine, and fecal electrolyte and mineral concentrations differ between clinically normal horses and Thoroughbreds with recurrent exertional rhabdomyolysis (RER) after consumption of diets varying in cation-anion balance. ANIMALS: 5 Thoroughbred mares with RER and 6 clinically normal mixed-breed mares. PROCEDURE: Each of 3 isocaloric diets designated as low, medium, and high on the basis of dietary cation-anion balance (DCAB) values of 85, 190, and 380, respectively, were fed to horses for 14 days. During the last 72 hours, 3 horses with RER and 3 control horses had daily urine and fecal samples obtained by total 24-hour collection. Remaining horses had urine samples collected daily by single catheterization. RESULTS: For each diet, no differences existed between horses with RER and control horses in plasma pH, electrolyte concentrations, and creatine kinase activity or in urine pH and renal fractional excretion (FE) values. Plasma pH, strong ion difference, bicarbonate and total carbon dioxide concentrations, and base excess decreased and plasma chloride and ionized calcium concentrations increased with decreasing DCAB. Urine pH decreased with decreasing DCAB. The FE of chloride and phosphorus were greatest for horses fed the low diet. The FE values for all electrolytes exept magnesium did not differ between urine samples obtained by single catheterization and total 24-hour collection. Daily balance of calcium, phosphorus, sodium, chloride, and potassium did not differ significantly among horses fed the various diets. CONCLUSIONS: In clinically normal horses and in horses with RER, the DCAB strongly affects plasma and urine pH and the FE of sodium, potassium, chloride, and phosphorus.

Animal Feed↗

Exclusion of linkage of the RYR1, CACNA1S, and ATP2A1 genes to recurrent exertional rhabdomyolysis in Thoroughbreds.

OBJECTIVE: To determine whether there was genetic linkage between the recurrent exertional rhabdomyolysis (RER) trait in Thoroughbred horse pedigrees and DNA markers in genes (the sarcoplasmic reticulum calcium release channel [RYR1] gene, the sarcoplasmic reticulum calcium ATPase [ATP2A1] gene, and the transverse tubule dihydropyridine receptor-voltage sensor [CACNA1S] gene) that are important in myoplasmic calcium regulation. ANIMALS: 34 horses in the University of Minnesota RER resource herd and 62 Thoroughbreds from 3 families of Thoroughbreds outside of the university in which RER-affected status was assigned after 2 or more episodes of ER had been observed. PROCEDURES: Microsatellite DNA markers from the RYR1, ATP2A1, and CACNA1S gene loci on equine chromosomes 10, 13, and 30 were identified. Genotypes were obtained for all horses in the 4 families affected by RER, and data were used to test for linkage of these 3 loci to the RER phenotype. RESULTS: Analysis of the RYR1, CACNA1S, and ATP2A1 microsatellites excluded a link between those markers and the RER trait. CONCLUSIONS AND CLINICAL RELEVANCE: It is likely that the heritable alterations in muscle contractility that are characteristic of RER are caused by a gene that is not yet known to cause related muscle disease in other species.

Animals↗

Inheritance of recurrent exertional rhabdomyolysis in thoroughbreds.

OBJECTIVE: To develop a diagnostic test for recurrent exertional rhabdomyolysis (RER) in Thoroughbreds that relied on in vitro contracture of muscle biopsy specimens and determine whether the inheritance pattern of RER diagnosed on the basis of this contracture test was consistent with an autosomal dominant trait. DESIGN: Clinical trial. ANIMALS: 8 adult horses with RER and 16 control adult horses for development of the contracture test; 23 foals for inheritance of RER. PROCEDURE: External intercostal muscle biopsy specimens from the 24 adult horses were tested for contracture in response to halothane and caffeine, and criteria for a positive test result were determined. These criteria were then applied to results for the 23 foals to determine whether they had RER. Simple segregation analysis was performed to determine whether results were consistent with a dominant pattern of inheritance. RESULTS: Results of the contracture test were positive for 5 of the 12 colts and 4 of the 11 fillies. Results of segregation analysis were consistent with an auto-. somal dominant pattern of inheritance. Two sires with RER produced colts with RER, supporting the hypothesis that RER had an autosomal, rather than an X-linked, inheritance pattern. In addition, in 1 instance, an unaffected colt was produced by 2 affected parents, which was not consistent with a recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: Although the expression of the RER trait is influenced by sex, temperament, and diet, among other factors, results from the in vitro muscle contracture test and this breeding trial suggest that RER in Thoroughbreds can be modeled as a genetic trait with an autosomal dominant pattern of inheritance.

Anesthetics, Inhalation↗

A new method for prescribing exercise: three-point ratings of perceived exertion.

An accurate exercise prescription for ratings of perceived exertion has previously depended on data from a maximal graded exercise test during which RPE was measured. In many clinical settings RPE is not measured; in many fitness settings maximal testing is not feasible. A new method using treadmill speed or power output of a cycle ergometer at an RPE of 13 from a submaximal test which can be used in these situations is described. We evaluated the accuracy of this method at 50%, 60%, 70%, and 85% VO2max. A total of 160 target RPEs were developed using traditional procedures and the new method. No significant differences between RPEs obtained with the two techniques were found. The mean difference was less than one unit of RPE. It appears that the new method is valid for intensities of 50% to 85% VO2max and that data from either the cycle ergometer or the treadmill can be used to prepare exercise prescriptions.

Adult↗

Psychological affect at different ratings of perceived exertion in high- and low-active women: a study using a production protocol.

The purpose of this study was to examine psychological affect at different ratings of perceived exertion (RPE) in 15 high- and 15 low-active women. Both groups performed three steady-state exercise bouts on a cycle ergometer at RPEs 9, 13, and 17 and reported their affect in the last 20 sec. of and 5 min. after each work rate. There were no differences between groups in percentage of maximal oxygen uptake (% VO2max) at each RPE. Low-active women reported feeling significantly more negative at RPE 17 than RPE 9 and less positive than the high-active women at RPEs 9, 13, and 17. In addition, all subjects reported more positive feelings 5 min. postexercise than in the last 20 sec. of exercising, especially at RPE 17. These results have implications for exercise prescription in groups differing in habitual activity levels.

Adolescent↗

Validity of the Borg perceived exertion scale for use in semirecumbent ergometry during immersion in water.

This investigation examined the validity of the Borg 15-category Ratings of Perceived Exertion (RPE) scale during semirecumbent exercise in 32 degrees C water. 9 men undertook 12 8-min. trials at 3 power outputs and 4 pedal-crank rates. The power output was distributed between the arms (20%) and legs (80%). RPEs were measured for the arms, legs, chest, and over-all body. Correlation coefficients for RPE expressed as a function of power output and gross metabolic efficiency (MEG) ranged from .56 to .83 and .54 to .70, respectively, for each pedal-crank rate. Validity coefficients were greatest at those pedal-crank rates having the highest MEG. The Borg 15-category RPE scale is valid for use during semirecumbent exercise in water.

Adult↗

Diazepam inhibits phagocytosis and killing exerted by polymorphonuclear cells and monocytes from healthy donors. In vitro studies.

The effect of a benzodiazepine (BDZ), diazepam on human polymorphonuclear cell (PMN) and monocyte phagocytosis and killing from healthy volunteers has been evaluated. Diazepam is able to inhibit in vitro both functions exerted by PMN and monocytes at 10(-5) and 10(-6) M concentrations/ 4 x 10(6) phagocytes. 10(-7) M concentration was not effective in all the instances. These results are discussed for their possible clinical implications, since previous studies have shown that in patients with phobic disorder there is evidence for reduced phagocytosis and killing capacities.

Adult↗