The Infectious Diseases Act and Resource Allocation during the COVID-19 Pandemic in Bangladesh.

The Infectious Diseases (Prevention, Control and Eradication) Act entered into force officially on 14 November 2018 in Bangladesh. The Act is designed to raise awareness of, prevent, control, and eradicate infectious or communicable diseases to address public health emergencies and reduce health risks. A novel coronavirus disease (COVID-19) was first identified in Bangladesh on 8 March 2020, and the Ministry of Health and Family Welfare issued a gazette on 23 March, listing COVID-19 as an infectious disease and addressing COVID-19 as a public health emergency. The gazette empowers the government to monitor the spread of infection. Despite there being an infrastructure of research ethics committees in almost all hospitals in Bangladesh, a lack of such committees in the clinical setting often forces healthcare professionals to allocate scarce healthcare resources to the task. These personnel are often either influenced by materialistic matters or guided by the emergency policies, without reaching a consensus on how to allocate scarce resources in times of need, especially in the time of the COVID-19 pandemic. Ethical dilemmas often arise when a number of patients with COVID-19, especially in poor and middle-class areas, are denied care while elites are prioritized to receive such scarce resources. Resource allocation in healthcare during the COVID-19 pandemic in Bangladesh appears to be unethical and in direct conflict with the biomedical principles of non-maleficence and procedural justice. The findings of this study suggest that the Act needs substantive changes in the stipulation of policy directing hospitals in the provision of resource allocation framework. Furthermore, parliament should produce guidance outlining how to successfully implement the law with the aim of protecting public health in times of emergency, especially the COVID-19 pandemic.

Mathematical Global Dynamics and Control Strategies on Echinococcus multilocularis Infection.

Echinococcus multilocularis, a major cause of echinococcosis in human, is a parasitic sylvatic disease between two major hosts in a predator-prey relation. A new model for the transmission dynamics of Echinococcus multilocularis in the population of red foxes and voles with environment as a source of infection is formulated and rigorously analyzed. The model is used to access the impact of treatment on red foxes and environmental disinfection as control strategies on the disease dynamics. The control reproduction number is computed and is used to rigorously prove the local and global dynamics of models' equilibria. Using available data on Echinococcus, elasticity indices and partial rank correlation coefficients of control reproduction number and cumulative new cases in red foxes and voles are computed. Parameters that have high influence locally and globally are identified. Numerical experiments indicate that administering disinfection of environment only induces more positive impact than applying treatment only on red foxes in controlling the infection. Generally, interventions towards treating red foxes and environmental disinfection could be sufficient in tackling transmission of disease in the populations.

Toll-like receptor (TLR)7 expression in mycosis fungoides and psoriasis: a case-control study.

BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions. METHODS: This case-control study enrolled 28 patients with MF: 30 patients with psoriasis, and 30 age- and sex-matched healthy controls (HCs). A 4-mm punch skin biopsy was obtained from lesional skin of patients and from normal skin of HCs for detection of TLR7 gene expression using real-time PCR. RESULTS: Mean TLR7 level in patients with MF (0.4 ± 0.23) was significantly lower than in patients with psoriasis (1.49 ± 0.46) and in HCs (1.22 ± 0.44) (P < 0.001), and mean TLR7 level in patients with psoriasis was significantly higher than in HCs (P < 0.03). Based on MF staging, 21.4% of patients had stage Ia, 28.6% had stage Ib, 28.6% had stage IIa and 21.4% had stage IIb disease. Comparing the TLR7 levels in relation to MF staging revealed the lowest mean value was in stage IIb and highest mean value in stage Ia, and this was significant (P < 0.001). CONCLUSION: Disturbed innate immunity might play a role in the pathogenesis of neoplastic and inflammatory skin conditions. TLR7 could be useful as a prognostic factor in MF.

Dynamics of Mycobacterium and bovine tuberculosis in a human-buffalo population.

A new model for the transmission dynamics of Mycobacterium tuberculosis and bovine tuberculosis in a community, consisting of humans and African buffalos, is presented. The buffalo-only component of the model exhibits the phenomenon of backward bifurcation, which arises due to the reinfection of exposed and recovered buffalos, when the associated reproduction number is less than unity. This model has a unique endemic equilibrium, which is globally asymptotically stable for a special case, when the reproduction number exceeds unity. Uncertainty and sensitivity analyses, using data relevant to the dynamics of the two diseases in the Kruger National Park, show that the distribution of the associated reproduction number is less than unity (hence, the diseases would not persist in the community). Crucial parameters that influence the dynamics of the two diseases are also identified. Both the buffalo-only and the buffalo-human model exhibit the same qualitative dynamics with respect to the local and global asymptotic stability of their respective disease-free equilibrium, as well as with respect to the backward bifurcation phenomenon. Numerical simulations of the buffalo-human model show that the cumulative number of Mycobacterium tuberculosis cases in humans (buffalos) decreases with increasing number of bovine tuberculosis infections in humans (buffalo).

Pediatric kidney transplantation in the developing world: challenges and solutions.

The prevalence of pediatric RRT and transplantation are low in developing countries, 6-12 and <1 to 5 per million child population (pmcp), respectively. This is due to low GDP/capita of <$10 000, government expenditure on health of <2.6-9% of GDP and paucity of facilities. The reported incidence of pediatric CKD and ESRD is <1.0-8 and 3.4-35 pmcp, respectively. RRT and transplantation are offered mostly in private centers in cities where HD costs $20-100/session and transplants $10 000-20 000. High costs and long distance to centers results in treatment refusal in up to 35% of the cases. In this backdrop 75-85% of children with ESRD are disfranchised from RRT and transplantation. Our center initiated an integrated dialysis-transplant program funded by a community-government partnership where RRT and transplantation was provided "free of cost" with life long follow-up and medication. Access to free RRT at doorsteps and transplantation lead to societal acceptance of transplantation as the therapy of choice for ESRD. This enabled us to perform 475 pediatric transplants in 25 years with 1- and 5-year graft survival of 96% and 81%, respectively. Our model shows that pediatric transplantation is possible in developing countries when freely available and accessible to all who need it in the public sector.

Anti-inflammatory activity of crude saponin extracts from five Nigerian medicinal plants.

Crude saponin extracts of five medicinal plants used in the treatment of inflammatory diseases like rheumatoid arthritis, gout and haemorrhoids were screened for anti-inflammatory activity using carrageenan-induced rat paw oedema test. These plants were the whole plant of Schwenkia americana Linn (WSA), the rhizomes of Asparagus africanus Lam (RAA), the leaves of Dichrostachys cinerea Linn (LDC), the stem bark of Ficus iteophylla Miq (BFI) and the leaves of Indigofera pulchra Willd (LIP). A modify traditional method of crude saponins extraction was used to give the following percentage yields: WSA-2.74%, RAA-3.59%, LDC-1.62%, BFI-0.81% and LIP-1.57% respectively. Thin-layer chromatography was used to identify the type of saponins present in the extracts. The acute toxicity study of the crude saponin extracts in mice gave the following intraperitoneal LD50: WSA-471.2mg/kg, RAA- 1264.9mg/kg, LDC-1264.9 mg/kg, BFI-118.3mg/kg and LIP-1264.9 mg/kg respectively. The anti-inflammatory study of the extracts showed statistically significant (P<0.05) decreases in the rat paw-oedema as compared to the control. The percentage inhibitions of the extracts after four hours were as follow: WSA-61%, RAA-55%, LDC-72%, BFI-66% and LIP-40% respectively. These values were found to be comparable to that of ketoprofen-63%. The study showed that the anti-inflammatory properties attributable to these plants may be due to their saponins contents.

Toll-like receptor 2 is highly expressed in lesions of acne inversa and colocalizes with C-type lectin receptor.

BACKGROUND: Acne inversa (hidradenitis suppurativa) is a chronic inflammatory and cicatricial disorder that affects skin areas rich in apocrine glands and terminal hairs, such as perineum and axillae. The exact pathogenesis of the disease is not well understood and the mechanisms by which bacterial superinfection contributes to the disease progression are not clear. Toll-like receptors (TLRs) expressed by inflammatory cells play a crucial role in the innate immune response to bacteria. OBJECTIVES: We sought to investigate the role of TLR2 in the pathogenesis of acne inversa. METHODS: We investigated the expression of TLR2 using real-time polymerase chain reaction analysis and immunohistochemical stainings of tissue samples from patients with acne inversa. Furthermore, we phenotypically characterized the infiltrating cells and their expression of TLR2. RESULTS: Compared with normal skin, a highly increased in situ expression of TLR2 in acne inversa skin lesions was found at both the mRNA and the protein level. The most abundant cells in the dermal infiltrate of acne inversa were CD68+ macrophages, CD209+ dendritic cells (DCs) and CD3+ T cells. CD19+ B cells and CD56+ natural killer cells were found only in small numbers. Double staining with fluorescence-labelled antibodies showed that TLR2 was expressed by infiltrating macrophages (CD68+) and DCs (CD209+). Flow cytometric analysis of isolated infiltrating cells further confirmed surface expression of TLR2 by macrophages and DCs. CONCLUSIONS: These data indicate that the enhanced expression of TLR2 by infiltrating macrophages and DCs may contribute to the pathogenesis of inflammatory lesions of acne inversa.

Analgesic and anti-inflammatory activities of Asparagus africanus root extract.

The methanolic extract of the roots of Asparagus africanus Lam (Liliaceae) which contains mainly saponins and carbohydrate showed significant analgesic and anti-inflammatory activities (P<0.05) in the tail-flick/hot-plate test and egg albumen-induced rat paw oedema tests that were comparable to the test drugs (morphine 20 mg/kg and indomethacin 50 mg/kg respectively). These results indicate that the extract possesses analgesic and anti-inflammatory properties.

Analgesic and Anti-Inflammatory Activities of Asparagus Africanus Root Extract

The methanolic extract of the roots of Asparagus africanus Lam (Liliaceae) which contains mainly saponins and carbohydrate showed significant analgesic and anti-inflammatory activities (P0.05) in the tail-flick/hot-plate test and egg albumen-induced rat paw oedema tests that were comparable to the test drugs (morphine 20mg/kg and indomethacin 50mg/kg respectively). These results indicate that the extract possesses analgesic and anti-inflammatory properties

Hyperhydration prior to a simulated second day of the 3-day moderate intensity equestrian competition does not cause arterial hypoxemia in Thoroughbred horses.

Dehydration and the associated impairment of cardiovascular and thermoregulatory function comprise major veterinary problems in horses performing prolonged exercise, particularly under hot and humid conditions. For these reasons, there is considerable interest in using pre-exercise hyperhydration to help maintain blood volume in the face of the excessive fluid loss associated with sweat production during prolonged exertion. However, recently it was reported that pre-exercise hyperhydration causes arterial hypoxemia in horses performing moderate intensity exercise simulating the second day of an equestrian 3-day event competition (E3DEC) which may adversely affect performance (Sosa Leon et al. in Equine Vet J Suppl 34:425-429, 2002). These findings are contrary to data from horses performing short-term maximal exertion, wherein hyperhydration did not affect arterial O2 tension/saturation. Thus, our objective in the present study was to examine the impact of pre-exercise hyperhydration on arterial oxygenation of Thoroughbred horses performing an exercise test simulating the second day of an E3DEC. Control and hyperhydration studies were carried out on seven healthy Thoroughbred horses in random order, 7 days apart. In the control study, horses received no medications. In the hyperhydration experiments, nasogastric administration of NaCl (0.425 g/kg) 5 h pre-exercise induced a plasma volume expansion of 10.9% at the initiation of exercise. This methodology for inducing hypervolemia was different from that of Sosa Leon et al. (2002). Blood-gas tensions/pH as well as plasma protein, hemoglobin and blood lactate concentrations were measured pre-exercise and during the exercise test. Our data revealed that pre-exercise hyperhydration neither adversely affected arterial O2 tension nor hemoglobin-O2 saturation at any time during the exercise test simulating the second day of an E3DEC. Further, it was observed that arterial blood CO2 tension, pH, and blood lactate concentrations also were not affected by pre-exercise hyperhydration. However, hemodilution in hyperhydrated horses caused an attenuation of the expansion in the arterial to mixed-venous blood O2 content gradient during phases B and D of the exercise protocol, which was likely offset by an increase in cardiac output. It is concluded that pre-exercise hyperhydration of horses induced in the manner described above is not detrimental to arterial oxygenation of horses performing an exercise test simulating the second day of an E3DEC.

The efficacy of excimer laser (308 nm) for vitiligo at different body sites.

BACKGROUND: The treatment with XeCl-excimer laser generated 308-nm UVB radiation has shown promising results in patients with vitiligo. OBJECTIVE: In this controlled, prospective trial we studied the primary efficacy (start and grade of repigmentation) and patient's satisfaction of XeCl-excimer laser for treatment of vitiligo patches at different body sites and re-evaluated the achieved repigmentation 12 months after the end of therapy. METHODS: Twenty-five patients with generalized or localized vitiligo with a total of 85 lesions at different body sites were enrolled in this study. Vitiligo patches were treated with 308-nm XeCl-excimer laser 3 times a week for 6 to 10 weeks. The overall repigmentation grade of each treated lesion was evaluated once a week on a 5 point scale rating from 0 (no repigmentation), 1 (1-5%), 2 (6-25%), 3 (26-50%), 4 (51-75%), to 5 (76-100%). RESULTS: Twenty-four patients completed the study. Within 6 to 10 weeks of treatment 67% of the patients (16/24) developed follicular repigmentation of at least one of their vitiligo lesions. Lesion repigmentation started after a mean of 13 treatments in lesions located on the face, trunk, arm, and/or leg (high-responder location), and after a mean of 22 treatments in lesions located on the elbow, wrist, dorsum of the hand, knee, and/or dorsum of the foot (low-responder location). Untreated control lesions and lesions located on the fingers did not achieve any repigmentation. After 10 weeks of treatment repigmentation of more than 75% was found in 25% (7/28) of lesions of the high-responder location group versus 2% (1/43) of lesions of the low-responder location group. In most cases, laser-induced repigmentation was persistent, as determined 12 months after the end of treatment. CONCLUSIONS: 308-nm excimer laser is an effective modality for the treatment of vitiligo. However, similar to other non-surgical treatment modalities, the therapeutic effect is mainly dependent on the location of vitiligo lesions.

Nitric oxide synthase inhibition in thoroughbred horses augments O2 extraction at rest and submaximal exercise, but not during short-term maximal exercise.

REASON FOR PERFORMING STUDY: Work is required to establish the role of endogenous nitric oxide (NO) in metabolism of resting and exercising horses. OBJECTIVES: To examine the effects of NO synthase inhibition on O2 extraction and anaerobic metabolism at rest, and during submaximal and maximal exertion. METHODS: Placebo and NO synthase inhibition (with Nomega-nitro-L-arginine methyl ester [L-NAME] administered at 20 mg/kg bwt i.v.) studies were performed in random order, 7 days apart on 7 healthy, exercise-trained Thoroughbred horses at rest and during incremental exercise leading to 120 sec of maximal exertion at 14 m/sec on a 3.5% uphill grade. RESULTS: At rest, NO synthase inhibition significantly augmented the arterial to mixed-venous blood O2 content gradient and O2 extraction as mixed-venous blood O2 tension and saturation decreased significantly. While NO synthase inhibition did not affect arterial blood-gas tensions in exercising horses, the exercise-induced increment in haemoglobin concentration and arterial O2 content was attenuated. In the L-NAME study, during submaximal exercise, mixed-venous blood O2 tension and haemoglobin-O2 saturation decreased to a greater extent causing O2 extraction to increase significantly. During maximal exertion, arterial hypoxaemia, desaturation of haemoglobin and hypercapnia of a similar magnitude developed in both treatments. Also, the changes in mixed-venous blood O2 tension and haemoglobin-O2 saturation, arterial to mixed-venous blood O2 content gradient, O2 extraction and markers of anaerobic metabolism (lactate and ammonia production, and metabolic acidosis) were not different from those in the placebo study. CONCLUSION: Endogenous NO production augments O2 extraction at rest and during submaximal exertion, but not the during short-term maximal exercise. Also, NO synthase inhibition does not affect anaerobic metabolism at rest or during exertion. POTENTIAL RELEVANCE: It is unlikely that endogenous NO release modifies aerobic or anaerobic metabolism in horses performing short-term maximal exertion.

Pre-exercise hypervolaemia is not detrimental to arterial oxygenation of horses performing a prolonged exercise protocol simulating the second day of a 3-day equestrian event.

REASONS FOR PERFORMING STUDY: Hyperhydration, prior to prolonged moderate-intensity exercise simulating the 2nd day of a 3-day equestrian event (E3DEC), may induce arterial hypoxaemia detrimental to performance. OBJECTIVES: Because moderate-intensity exercise does not induce arterial hypoxaemia in healthy horses, the effects of pre-exercise hypervolaemia on arterial oxygenation were examined during a prolonged exercise protocol. METHODS: Blood-gas studies were carried out on 7 healthy, exercise-trained Thoroughbred horses in control and hyperhydration experiments. The study conformed to a randomised crossover design. The sequence of treatments was randomised for each horse and 7 days were allowed between studies. Hyperhydration was induced by administering 0.425 g/kg bwt NaCl via nasogastric tube followed by free access to water. The exercise protocol was carried out on a treadmill set at a 3% uphill grade and consisted of walking at 2 m/sec for 2 min, trotting for 10 min at 3.7 m/sec, galloping for 2 min at 14 m/sec (which elicited maximal heart rate), trotting for 20 min at 3.7 m/sec, walking for 10 min at 1.8 m/sec, cantering for 8 min at 9.2 m/sec, trotting for 1 min at 5 m/sec and walking for 5 min at 2 m/sec. RESULTS: NaCl administration induced a significant mean +/- s.e. 15.5 +/- 1.1% increase in plasma volume as indicated by a significant reduction in plasma protein concentration. In either treatment, whereas arterial hypoxaemia was not observed during periods of submaximal exercise, short-term maximal exertion caused significant arterial hypoxaemia, desaturation of haemoglobin, hypercapnoea, and acidosis in both treatments. However, the magnitude of exercise-induced arterial hypoxaemia, desaturation of haemoglobin, hypercapnoea, and acidosis in both treatments remained similar, and statistically significant differences between treatments could not be demonstrated. CONCLUSIONS: It was concluded that significant pre-exercise expansion of plasma volume by this method does not adversely affect the arterial oxygenation of horses performing a prolonged exercise protocol simulating the 2nd day of an E3DEC.

Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients.

BACKGROUND: Recently the beneficial effect of excimer laser treatment has been reported for patients with vitiligo. The influence of treatment frequency on this effect is not clear. OBJECTIVES: To determine the optimal frequency of 308-nm excimer laser therapy for vitiligo. METHODS: In this prospective, university-based hospital study over 12 weeks we enrolled 14 patients. Each had at least three stable vitiligo lesions in the same body area. The three stable vitiligo lesions in each subject were randomly assigned to receive excimer laser treatment once (1 x), twice (2 x) and three times (3 x) weekly, respectively. The initial ultraviolet (UV) dose was 50 mJ cm(-2) less than the 308-nm minimal erythematous dose in vitiligo skin. The UV dose was increased at each treatment session according to the erythematous response to the previous treatment. RESULTS: Thirteen subjects were treated for at least 6 weeks; seven were treated for all 12 weeks. At 6 weeks, the repigmentation rates for treated lesions were 8% (1/13) after 1 x weekly treatment, 23% (3/13) after 2 x weekly treatment and 62% (8/13) after 3 x weekly treatment (P = 0.0134; 3 x vs. 1 x weekly); at 12 weeks, these rates were 46% (6/13), 62% (8/13) and 69% (9/13), respectively (P = NS; 3 x vs. 1 x weekly). Repigmentation initiation correlated with treatment number, regardless of frequency (P = NS). As shown by Kaplan-Meier analysis, repigmentation occurred earliest in the most frequently treated lesions (P = 0.0336). At 12 weeks, the projected repigmentation rates for 1 x, 2 x and 3 x weekly treatment approached each other (60%, 79% and 82%, respectively); the mean repigmentation grades (on a scale of 0-5) for 1 x, 2 x and 3 x weekly treatment were 1.7, 2.4 and 3.3, respectively (P = 0.018; 3 x vs. 1 x weekly). Laser-induced repigmentation persisted in most cases over the entire follow-up of 12 months after the end of treatment. CONCLUSIONS: 308-nm excimer laser therapy is effective against vitiligo. Although repigmentation occurs fastest with 3 x weekly treatment, the ultimate repigmentation initiation seems to depend entirely on the total number of treatments, not their frequency. However, treatment periods of more than 12 weeks may be necessary to obtain a satisfactory clinical repigmentation, particularly when vitiligo lesions are treated only 1 x or 2 x compared with 3 x weekly.

[Dyschromatosis universalis hereditaria. An unusually rare clinical picture]. / Dyschromatosis universalis hereditaria. Ein aussergewöhnlich seltenes klinisches Bild.

A 30-year old male patient presented with a rare congenital pigment disturbance, dyschromatosis universalis hereditaria. Clinically, he displayed mottled hyperpigmentation covering almost the entire skin surface with accentuation in skin folds. The lesions had been present since birth. He was the only family member showing these changes. He had no other medical problems and took no medications.

Inhibition of nitric oxide synthase with L-NAME does not increase lactate production at rest or during short-term high-intensity exercise in Thoroughbred horses.

The present study was carried out to determine whether inhibition of nitric oxide (NO) synthase promotes anaerobic metabolism in exercising horses, resulting in a significantly increased blood lactate concentration. N(omega)-nitro-L-arginine methyl ester (L-NAME) is a potent inhibitor of NO synthase that has been tested in horses and other species. Two sets of experiments, namely placebo (saline control) and L-NAME (20 mg/kg, i.v.) studies, were carried out on seven healthy, sound, exercise-trained, Thoroughbred horses in random order, 6 to 7 days apart. In both experiments, an incremental exercise protocol was used and data were obtained at rest, during submaximal exercise performed at 8 m/s on a 4.5% uphill grade, and during galloping at 14 m/s on a 4.5% uphill grade--a workload that not only elicited maximal heart rate and induced exercise-induced pulmonary haemorrhage, but also could not be sustained for more than 90 s. Measurements were also made in the recovery period. Mixed-venous blood samples, obtained at matched intervals in the two sets of experiments, were analysed in triplicate for determining the lactate concentration. Following administration of L-NAME, significant bradycardia occurred at rest (27 +/- 1 vs 37 +/- 2 beats/min in the placebo trials; p<0.0001) as well as during submaximal exercise (183 +/- 4 vs 200 +/- 4 beats/min in the placebo trials; p<0.001), but the heart rate increased during galloping at 14 m/s on a 4.5% uphill grade to reach values observed in the placebo trials (215 +/- 2 beats/min) and significant differences were not found. At rest, the mixed-venous blood lactate concentration was similar in the two experiments. With exercise, the mixed-venous blood lactate concentration increased progressively as work intensity increased in both trials, but significant differences were not found between the placebo and the L-NAME experiments during submaximal exercise, near-maximal exercise or recovery. These experiments demonstrated that inhibition of NO synthase in Thoroughbred horses does not promote enhanced anaerobic metabolism at rest or during short-term incremental exercise leading to galloping at maximal heart rate.

Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses.

Because sensitivity of equine pulmonary vasculature to endogenous as well as exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous NO production plays a role in exercise-induced arterial hypoxemia. We hypothesized that inhibition of NO synthase may alter the distribution of ventilation-perfusion mismatching, which may affect the exercise-induced arterial hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound Thoroughbred horses at rest and during incremental exercise protocol leading to galloping at maximal heart rate without (control; placebo = saline) and with N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (20 mg/kg iv). The experiments were carried out in random order, 7 days apart. At rest, L-NAME administration caused systemic hypertension, pulmonary hypertension, and bradycardia. During 120 s of galloping at maximal heart rate, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and acidosis occurred in the control as well as in NO synthase inhibition experiments. However, statistically significant differences between the treatments were not found. In both treatments, exercise caused a significant rise in hemoglobin concentration, but the increment was significantly attenuated in the NO synthase inhibition experiments, and, therefore, arterial O(2) content (Ca(O(2))) increased to significantly lower values. These data suggest that, whereas L-NAME administration does not affect pulmonary gas exchange in exercising horses, it may affect splenic contraction, which via an attenuation of the rise in hemoglobin concentration and Ca(O(2)) may limit performance at higher workloads.