Risk factors for severe disease in pediatric respiratory syncytial virus infections.

OBJECTIVES: To assess factors associated with the risk of severe disease in children aged 5 years or younger with laboratory-confirmed respiratory syncytial virus (RSV) infection. STUDY DESIGN: We conducted a nationwide retrospective cohort study in Mexico. METHODS: Eligible participants included children aged 5 years or younger with laboratory-confirmed RSV infection January 1, 2023, and May 15, 2024. We collected relevant clinical and epidemiological data. Risk ratios (RR) and 95% confidence intervals (CI) were employed to identify factors associated with the risk of severe disease, characterized by clinical and radiographic evidence of bronchiolitis or pneumonia requiring hospital admission. RESULTS: Data from 2022 children were analyzed and the overall risk of severe disease was 21.0% (n = 424/2022). In multiple generalized linear regression analysis, a personal history of immunosuppression (due to any cause) showed a protective effect (RR = 0.14, 95% CI 0.05-0.42, P = 0.001) against severe RSV disease, while an increased risk was documented for each additional day elapsed between the date of symptom onset and the date of seeking healthcare RR = 1.06, 95% CI 1.02-1.10, P = 0.004). CONCLUSION: These findings provide insights into risk stratification and suggest specific directions for future research. This information informs the development of targeted intervention strategies to mitigate the impact of RSV infections in this vulnerable population.

Respiratory syncytial virus infection: survival experience in a cohort of children inpatients.

OBJECTIVE: The objective of this study was to assess the survival experience of children hospitalized with laboratory-confirmed respiratory syncytial virus (RSV) infection due to bronchiolitis. STUDY DESIGN: This was a nationwide retrospective cohort study conducted in Mexico. METHODS: We analyzed data from 436 children aged 5 years and younger, with symptom onset between August 2021 and November 2022. The Kaplan-Meier method was used to compute survivor functions and their 95% confidence intervals (CI). RESULTS: High survival rates were observed, particularly within the first three weeks of hospital admission. The 3-day survival rate was 99.8% (CI 98.4-99.9%), which decreased to 98.9% (CI 96.5-99.7%), 97.5% (CI 91.9-99.3%), 86.7% (CI 48.2-97.2%), and 69.4% (CI 24.2-91.0%) on days 7, 14, 21, and 28 of hospital stay, respectively. We documented a total of 5 fatal outcomes, resulting in a mortality rate of 2.1 (95% CI 0.9-5.1) per 1,000 person-days. CONCLUSIONS: Our study analyzed a large cohort of pediatric patients with bronchiolitis caused by RSV infection, providing valuable insights into the in-hospital progression of this disease.

Evaluating the performance of WHO and CDC case definitions for influenza-like illness in diagnosing influenza during the 2022-2023 flu season in Mexico.

OBJECTIVE: This study aimed to evaluate the performance of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for influenza-like illness (ILI) in diagnosing influenza during the 2022-2023 flu season in Mexico. STUDY DESIGN: We conducted a cross-sectional analysis of national epidemiological surveillance data in Mexico, focusing on respiratory viral pathogens. METHODS: We analyzed data from 6027 non-hospitalized patients between 5 and 65 years old who underwent molecular testing for respiratory viral pathogens. The performance of both case definitions was evaluated in terms of sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve. RESULTS: Overall, the diagnostic accuracy of the evaluated ILI definitions in identifying influenza patients was low, particularly among older patients. When compared to the CDC, the WHO definition had a lower sensitivity but a higher specificity, resulting in a higher AUROC (P = 0.031) for the WHO criteria. CONCLUSIONS: Our findings suggest that the WHO and CDC ILI case definitions have limited accuracy for diagnosing influenza in non-hospitalized patients and highlight the need for more specific diagnostic tools to improve the detection of influenza cases during the flu season.

First-generation BNT162b2 and AZD1222 vaccines protect from COVID-19 pneumonia during the Omicron variant emergence.

OBJECTIVE: This study aimed to identify factors predicting pneumonia in adults with coronavirus disease 2019 (COVID-19) during the Omicron variant (B.1.1.529) emergence. We also evaluated, in fully vaccinated (BNT162b2 or AZD1222) individuals, if the time (<6 or ≥6 months) elapsed since the last shot was received was associated with the risk of severe illness. STUDY DESIGN: A retrospective cohort study was conducted in Mexico. METHODS: Data from 409,493 were analyzed, and risk ratios (RRs) and 95% confidence intervals (CIs) were computed through generalized linear models. RESULTS: We documented a total of 3513 COVID-19 pneumonia cases (69.5 per 100,000 person-days). In multiple analyses, a protective effect was observed in vaccinated adults (RR = 0.996, 95% CI 0.995-0.997). Male gender, increasing age, and smoking were associated with a greater risk of pneumonia. Individuals with chronic comorbidities (pulmonary obstructive disease, type 2 diabetes mellitus, arterial hypertension, kidney disease, and immunosuppression) were also at higher risk. Among fully vaccinated subjects (n = 166,869), those who had received the last shot at 6 more months were at increased risk for developing pneumonia (RR = 1.002, 95% CI 1.001-1.003). CONCLUSIONS: Our results suggest that the first-generation BNT162b2 and AZD1222 vaccines reduce the risk of COVID-19 pneumonia during the Omicron emergence. We also found that adults with longer interval from the administration of the second shot to illness onset were at increased risk of severe manifestations.

Decreased risk of COVID-19 pneumonia in children and adolescents during the Delta variant emergence.

OBJECTIVES: This study aimed to evaluate factors associated with the risk of COVID-19 pneumonia in children (aged <10 years) and adolescents (aged 10-19 years) before (March 2020-April 2021) and during (May-July 2021) the Delta (B.1.617.2) variant emergence. STUDY DESIGN: A retrospective and nationwide cohort study was conducted in Mexico. METHODS: Data from 26,961 laboratory-confirmed cases of COVID-19 were analyzed. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to evaluate the association of the evaluated exposures with the risk of COVID-19 pneumonia. RESULTS: The overall incidence rate of pneumonia was 23.0 per 10,000 person-days, and it was lower during the Delta variant emergence (30.3 vs. 9.4 person-days, p < 0.001). In multiple analysis, a decreased risk of pneumonia was observed among those cases occurring in May 2021 or later (vs. March 2020-April 2021, RR = 0.98, 95% CI 0.97-0.99) and among older patients (RRper year = 0.998, 95% CI 0.996-0.998). Other comorbidities (namely, obesity, chronic kidney disease, diabetes mellitus, immunosuppression, or malignant tumors) were associated with an increased risk of severe COVID-19 manifestations. CONCLUSIONS: Our findings suggest that during the Delta variant emergence, children and adolescent patients were at reduced risk of COVID-19 pneumonia in Mexico. Further research is needed to identify factors determining the observed scenario.

Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state.

Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (KATP) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoKATP channels). K+ channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 µM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD, 500 µM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoKATP channel opener but also as NO donor and as an antioxidant.

Cervical human papillomavirus infection in Mexican women with systemic lupus erythematosus or rheumatoid arthritis.

Cervical human papillomavirus (HPV+) infection is associated with an increased risk of cervical dysplasia. Although the frequency of HPV+ in systemic lupus erythematosus (SLE) has been investigated in some races its prevalence in Hispanic women is still unknown. This cross-sectional study evaluated the prevalence of cervical HPV+ in Mexican women with SLE (n = 34) or rheumatoid arthritis (RA) (n = 43) and in healthy controls (n = 146). These women were interviewed about risk factors for sexually transmitted infections and cervical cytology analysis was performed. HPV+ viral types were identified using PCR: HPV+ was observed in 14.7% of SLE, 27.9% of RA and 30.8% of controls. High-risk HPV types were observed in 11.7% of women with SLE, 27.9% of women with RA, and in 26% of the controls. High-risk viral types 58, 35 and 18 were the most frequently identified in SLE. Two women with SLE had a high-grade squamous intraepithelial lesion and one had cervical cancer. An association was observed between methotrexate utilization, longer duration of therapy with prednisone, and HPV+ in RA or SLE. Thus, there is a high prevalence of cervical HPV infection in Mexican women with SLE or RA, and physicians must be vigilant in preventing the development of cervical dysplasia.

Forskolin compared with beclomethasone for prevention of asthma attacks: a single-blind clinical trial.

This single-blind study compared the efficacy of oral forskolin versus inhaled beclomethasone for mild or moderately persistent adult asthma. Patients were randomly assigned to receive forskolin (one 10-mg capsule orally per day; n = 30) or beclomethasone (two 50 microg inhalations every 12 h; n = 30) for 2 months. No statistically significant improvement occurred in any lung function parameter in the forskolin-treated patients. Subjects in the beclomethasone-treated group presented a slight but statistically significant improvement in percentage forced expiratory volume in 1 s (FEV(1)), percentage forced expiratory flow in the middle (25 - 75%) expiratory phase (FEF(25 - 75%)) and percentage forced vital capacity (FVC) after 2 months of treatment, though the improvement in absolute values for FEV(1), FEF(25 - 75%), FVC and FEV(1):FVC did not reach statistical significance. There was no statistically significant difference between the forskolin and beclomethasone treatment groups for any lung function parameter at baseline or after treatment. None of the beclomethasone-treated patients had an asthma attack and one forskolin-treated patient had a mild asthma attack during the 2-month study period. More studies are needed in adult asthma patients to confirm whether forskolin may be a useful preventive treatment for mild or moderately persistent adult asthma.

Anthropometric and dietary differences among Mexican older adults with and without adequate body image perception.

OBJECTIVE: We compared anthropometric and dietary indicators between groups of older Mexican adults with accurate or inaccurate body image perception (BIP). METHODS: A cross-sectional study was carried out with 201 older adults (age ≥ 60 years) of both sexes who completed the Stunkard scale for BIP, which consists of nine silhouettes with an equivalent of body mass index (BMI) status, then, the accuracy with their real BMI was calculated and reported energy and macronutrient intake through a 24-h dietary recall directed by different geriatric centers in Colima, Mexico. Basic anthropometry and bioelectrical impedance analyses were performed. RESULTS: We found that 71.1% of the older adults had inaccurate BIP; 66.6% underestimated their body mass and 4.5% overestimated their body mass, the other 28.9% hat accurate BIP. The overall concordance between the real nutritional status and BIP was poor (kappa coefficient = 0.03). The inaccurate BIP group had a significantly higher mean body mass index, body fat percentage, muscle mass, and arm and calf circumference compared to the accurate BIP group (p < .001); only 4.3% of the older adults who were overweight and 6.2% who were obese had an accurate BIP. Regarding dietary consumption, we found significant differences only in energy and carbohydrate intake between the two groups. Finally, excess body fat was associated with an inaccurate BIP (OR: 2.8, 95% CI: 1.5-5.5). CONCLUSION: In older adults, an inaccurate BIP is generally associated with high anthropometric values and less than adequate dietary intake.

Sprint training attenuates the deficits of force and dynamic stiffness in rat soleus muscle caused by eccentric contractions.

We investigated whether sprint training attenuates the deficits in force and dynamic stiffness caused by eccentric contractions to the soleus muscles of Wistar rats. Two groups of male rats were analyzed: sedentary (C, n=8) and trained (T, n=8). T rats were sprint trained for 10 weeks. Subsequently, the right soleus muscles of rats were freed under anesthesia, leaving the bone insertion and blood supply intact. Eccentric contractions were induced by lengthening muscles during tetanic contractions. Force and dynamic stiffness were tested before and after 20 rounds of eccentric contractions. Tension decline was analyzed using a two-state model (first-order kinetics) in the context of Kramer's theory. Training improved the twitch tension (C, 6.44+/-0.6N/cm(2); T, 10.90+/-0.8N/cm(2)), tetanic force (C, 61.74+/-0.6N/cm(2); T, 85.62+/-0.8N/cm(2)), and increased the dynamic stiffness (C, 41.28+/-1.0N/cm(2); T, 49.56+/-3.2N/cm(2)). Twitch tension after eccentric contractions declined to 73% and 75% in C and T groups, respectively, while tetanic tension decreased to 60% and 36% in C and T groups, respectively. After eccentric contractions, dynamic stiffness decreases were smaller in T rats (from 49.56+/-3.2 to 36.09+/-2.1N/cm(2)) than in C rats (from 41.28+/-1.0 to 20.73+/-1.8N/cm(2)). Sprint training increased the dynamic stiffness and tetanic tension of the soleus muscle and protected against the attenuation induced by eccentric contractions. Finally, the two-state model provided evidence that the number of force-generating cross-bridges increases in trained muscle.

MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population.

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.

Forskolin versus sodium cromoglycate for prevention of asthma attacks: a single-blinded clinical trial.

To determine the efficacy of forskolin in preventing asthma attacks, we performed a single-blinded clinical study in children and adult out-patients at a public hospital in Mexico. Forty patients of either sex with mild persistent or moderate persistent asthma were assigned randomly to 6 months of treatment with forskolin at 10 mg/day orally (capsules) or with two inhalations of sodium cromoglycate every 8 h, i.e. three times a day. The number of patients who had asthma attacks during the treatment period was significantly lower among those receiving forskolin (8/20, 40%) than among those receiving sodium cromoglycate (17/20, 85%). Values of forced expiratory volume in 1 s and forced expiratory flow, mid-phase, A similar in the two groups during the treatment period. We conclude that forskolin is more effective than sod cromoglycate in preventing asthma attacks in patients with mild persistent or moderate persistent asthma.

Electrophysiological abnormalities in type 2 diabetic patients with reduced levels of insulin-like growth factor I.

This cross-sectional study investigated electrophysiological abnormalities in type 2 diabetics with normal and reduced insulin-like growth factor I (IGF-I) levels. Sixty patients and 20 non-diabetic controls were included in the study. The fasting serum glucose was measured and IGF-I levels were determined by radioimmunoassay in all patients. Nerve conduction tests were performed in all the study participants on the ulnar nerve and lower extremities. Compared with the controls, all the patients showed a reduction in the peak amplitude of the motor response, 58% showed a reduction in the motor conduction velocity and 55% showed a reduction in the sensory conduction velocity. There was no statistically significant correlation between the electrophysiological changes and the glucose or IGF-I levels. In conclusion, there does not appear to be a correlation between serum glucose or IGF-I levels and electrophysiological abnormalities in patients with type 2 diabetes mellitus.

Cannabinoids and dopamine receptors' action on calcium current in rat neurons.

OBJECTIVE: To study the effects of cannabinoid, glutamate, and dopamine agonists and antagonists on the calcium current rat sympathetic neurons. METHODS: Calcium current was recorded using the whole-cell variant of the patch-clamp technique. After expression in neuronal membranes of the cannabinoid CB1, glutamate mGluR2, or dopamine D1 receptor (by microinjection of the levant receptor's cDNA into the neuron's nucleus) agonists' and antagonists' effects were observed. RESULTS: Applications of agonists of the expressed receptor (0.1-10 microM) decreased the calcium current. The calcium current was increased after application of cannabinoid antagonists (AM251 and AM630); these compounds thus act as inverse agonists in this preparation. Glutamate and dopamine antagonists had no effects on the calcium current by themselves. Combined application of cannabinoids and dopamine, but not glutamate, agonists produced a decrement in the calcium current that was bigger than either of the effects seen when one agonist was applied alone. CONCLUSIONS: These results suggest that cannabinoid with dopamine receptors have an interactive inhibitory effect on the calcium current in this preparation, indicating that within the nervous system, receptor interactions may be important in the regulation of ion-channel functions.

COVID-19 mortality among pregnant women in Mexico: a retrospective cohort study

Background: Pregnant women have been classified as at risk for COVID-19 due to previous experience with influenza and other coronaviruses. The objective of this study was to identify risk factors for the complications and death in women of childbearing age and pregnant women with suspected COVID-19. Methods: This retrospective cohort study was conducted from the beginning of the epidemic in Mexico until May 25, 2020. All women of childbearing age (13-49 years) from the open national COVID-19 database from the Ministry of Health of Mexico were considered for eligibility. SARS-COV-2 infection was confirmed or ruled out by RT-qPCR. We performed a bivariate and multivariable analysis to estimate mortality risk. Results: Ten (2.2%) pregnant women with confirmed COVID-19 died. Positive pregnant patients did not have a higher risk of complications (admission to the ICU, pneumonia, or requirement for mechanical ventilation) or death than the controls. In the multivariate analysis, only history of diabetes and chronic kidney disease remained independently associated with death in the positive cohort. Seven (0.6%) pregnant women with a negative test died. In bivariate analysis, pregnant patients with a positive test had a higher risk of death than pregnant patients with a negative test (relative risk (RR) = 3.87, 95% confidence interval (CI) = 1.48-10.12), but no higher risk was found than in non-pregnant women with a positive test (RR = 0.82, 95% CI = 0.44-1.53), and 60-day mortality did not significantly differ among pregnant patients with or without a positive test (hazard ratio (HR) = 0.40, 95% CI = 0.12-1.30) or between COVID-19-positive patients who were pregnant or not pregnant (HR = 0.74, 95% CI = 0.35-1.56). Conclusions: Pregnant patients do not have a greater risk of complications or death from COVID-19 than non-pregnant patients. The presence of diabetes mellitus and chronic disease increases the risk of death in women of childbearing age, but not specifically in pregnant patients. (AU)

Effects of denervation on Ca2+ channels in slow skeletal muscle fibers of the frog.

Effects of denervation on calcium channels in slow skeletal muscle fibers in the frog (Rana pipiens) were studied using the three-microelectrode voltage-clamp technique in intact fibers. Ca2+, Ba2+, and Sr2+ currents were all significantly reduced in amplitude during the first 2 weeks after denervation. After nerve section the selectivity sequence Ba congruent with Ca > Sr was changed to Ba > Sr > Ca and the values for relative ratio increased from 1.04 to 2.65 for Ba2+ and from 0.58 to 1.20 for Sr2+ (with respect to Ca2+). Barium current saturation was more obvious in denervated fibers than in non-denervated fibers. The values obtained with the Michaelis-Menten type expression, I = Imax/(1+Kd/[Ba]e) were Kd = 2.7 mM and Imax = 20 microA/cm2 in fibers 2 weeks after nerve section compared with the values Kd = 4.4 mM and Imax = 60 microA/cm2 obtained in non-denervated fibers. Additionally, the effects of two calcium channel blockers (cobalt and nifedipine) were greater by a factor of two in denervated fibers than in non-denervated fibers. Three weeks or so after nerve section, all the biophysical properties studied began to show a tendency to recover toward the values obtained in non-denervated muscles (controls). These results suggest that calcium channels are modified or that there is a change in the types of calcium channels present in frog slow skeletal muscle fibers after denervation.

Measurement of Ca(2+) currents in intact slow skeletal muscle fibers of the frog by the three-microelectrode technique.

The recording of currents passing through calcium channels in intact skeletal muscle fibers presents several difficulties. However, use of the three-microelectrode voltage-clamp technique at the end of the fiber provided us with a good approximation of current values in such fibers. Using this technique, we were able to measure the calcium-channel current in slow skeletal muscle fibers of the frog (Rana pipiens) and to quantify the effects of denervation on this current.

Folding-unfolding of FN-III domains in tenascin: an elastically coupled two-state system.

In a single-molecule atomic force microscopy (AFM) experiment, the tenascin molecule is stretched by an external force causing an elongation which is due to the unfolding of the FN-III modules. The features of the force-extension curves depend on the pulling speed and show a saw-tooth pattern (lower speeds) or a smooth pattern (higher speeds). In any case, the unfolded domains are elastically coupled to the unfolded modules, acting as transmitters of the external force. In this communication, the folding-unfolding process of the FN-III domains in tenascin is studied using reaction rate theory and a simple two-state model. The main hypothesis of the study is that, at microscopic level, the force needed to unfold a domain and the unfolding rate (unfolding velocity) can mimic the macroscopic process of measurement by AFM. As the external force is applied, the probability of unfolding increases as dictated by the reaction rate theory. Within this context, a relationship between the unfolding force and the unfolding velocity is obtained. The latter relation will describe microscopically the process in a phenomenological fashion. Moreover, while relating the results of this study with other experimental (AFM measurements) and theoretical (Monte Carlo simulations) data, we found that the graph of unfolding force-unfolding velocity is similar to that of external force-pulling velocity. The refolding process can also be studied within this model and the results show similar trends. The latter suggests a generic and universal behavior of such kind of molecular domains at least in the light of the proposed model.

Adrenergic modulation of the K+ contractures in tonic skeletal muscle fibers of the frog.

The effects of adrenaline and isoprenaline on K+ contractures of curarized tonic skeletal fibers were investigated. The K+ contractures of tonic fibers have a peak tension followed by a sustained tension. The peak tension and total tension (the tension-time integral--area--of K+ contractures) were increased by adrenaline and isoprenaline. The resting potential of tonic skeletal fibers were unaffected by adrenaline. The calcium channel blocker (cadmium and nifedipine) greatly blocked the effects of adrenaline on the peak and total tension of K+ contractures. On the other hand, the peak and sustained tensions of K+ contractures were greatly reduced in Ca(2+)-free solution, but, the peak tension recovered when the fibers were pre-incubated in adrenaline. It is proposed that adrenergic modulation of tension in tonic skeletal muscle fibers could be related with the modulation of Ca2+ channels and/or Ca2+ release from the sarcoplasmic reticulum.

Caffeine and theophylline contractures in tonic skeletal muscle fibers of the frog.

Caffeine and theophylline evoke maintained tension in tonic skeletal muscle fibers of the frog. Their effects depended upon concentrations ranging from 0.5 to 14 mM. The resting potential of tonic skeletal fiber was unaffected by caffeine or theophylline (4 mM). Caffeine and theophylline contractures have a peak tension followed by a sustained tension, which recovered spontaneously when returned to normal solution. The peak tension and total tension (the area under tension-time curve) were reduced when the fibers were soaked in calcium-free solution. In addition the tension was reduced by calcium channel blockers (cadmium). The sustained tension was increased when external calcium was raised. These results suggest that caffeine and theophylline promote the calcium release from sarcoplasmic reticulum and probably the entry of calcium from external medium.