Thermographic Mapping of Arterial Perforators in the Leg.

Background: Preoperative localisation of perforators aids in easy intraoperative dissection. Infrared thermography is a simple, safe, and effective tool with a short learning curve that is useful in identifying perforators. It has been found to have a high concordance rate when compared with computed tomography angiography and is useful in identifying arterial perforators in the leg. Objectives: To create a thermographic map of arterial perforators in the leg and to determine the correlation between the number of perforators identified and the length of the leg. Materials and Methods: This was a cross-sectional study. The length of the leg was measured and the location of perforators corresponding to the distribution of the anterior tibial, posterior tibial, and peroneal arteries was identified using thermography. The mean number of perforators corresponding to the different surfaces of the leg was noted, this was then correlated with the length of the leg using the Pearson correlation coefficient. Results: Using thermography, perforators were identified along a line drawn from the medial malleolus to the medial tibia plateau and from the lateral malleolus to the head of the fibula and within 2 cm of these lines. More perforators were found in the middle third of the leg and there was no significant correlation between the number of perforators and the length of the leg. Conclusion: A useful surface marking to aid the identification of perforators in the leg using infrared thermography was found. There was no significant correlation between the length of the leg and the number of perforators.

The Impact of Covid-19 Pandemic on Acute Burn Admissions at the University College Hospital, Ibadan, Nigeria.

The coronavirus disease and the subsequent pandemic that followed drastically changed human civilization with disruptive effects on health and overall wellbeing of mankind. This disruptive effect has been shown to include changes in epidemiology of burn injuries. This study therefore aimed to determine the impact of covid-19 on acute burn presentation at the University College Hospital (UCH), Ibadan. This was a retrospective study carried out between April 1, 2019 and March 31, 2021. The period was divided into two: April 1, 2019 to March 31, 2020 and April 1, 2020 to March 31, 2021. Data obtained from the burn unit registry were analyzed using the Scientific Package For Social Sciences version 25. The only statistically significant finding from this study was the marked reduction in burn ICU admission during the pandemic (P < 0.001). A total of 144 patients presented to the burn intensive care unit at UCH, Ibadan during the period under review with 92 patients in the prepandemic year, and 52 patients in the pandemic year. Patient group from 0- to 9-year-olds representing 42% in prepandemic, and 30.8% in the pandemic period was the most affected age group. Scald was predominantly among the pediatric age group in both groups. Males were more likely to suffer flame burn in both study periods with a near gender equilibration during the pandemic. Burn injury during the pandemic resulted in more total body surface area burned. The lockdown effect of the pandemic resulted in a significant reduction in acute burn admissions at the UCH, Ibadan.

Pattern of childhood injury in a tertiary centre.

Introduction: Childhood injury and death have been projected to be a disease of public health significance, however, the trend in many developing countries of which Nigeria is one is still unknown. We, therefore, examine the pattern of childhood traumatic injury in our institution. Materials and Methods: The information of patients aged 16 years and below who presented with trauma was extracted from the trauma registry of the emergency units of University College Hospital, Ibadan, from 2015 to 2020. Data were analysed using the SPSS version 20. Results: A total of 3146 children were managed for trauma in the accident and emergency departments of the hospital. Most of them were males (61.2%) and within the under-five age group (36.4%). The majority of the injuries were secondary to fall (41.8%). Male child was more likely to be involved in any mechanism of injury and children between 11 and 16 years were commonly involved in machine hand injury (80%). Following intervention in the accident and emergency department, 44.1% were discharged in the emergency units, 21.5% required admission into the specialist ward, 6.0% died, 5.0% discharged against medical advice and 2.6% were referred. Conclusion: The burden of childhood injury is becoming significant thus demands more attention.

A review of some common African spices with antihypertensive potential.

Hypertension is the most common non-communicable disease, with about 1.28 billion hypertensive people worldwide. It is more prevalent in men than women and more common in the elderly. Hereditary, age, obesity, lifestyle, diet, alcohol, and chronic metabolic diseases are the major risk factors of hypertension. Treating hypertension is a complex process as there are several mechanisms responsible for its pathogenesis; hence, a combination of several drugs is used for managing hypertension. Drugs used in managing hypertension are expensive and often come with associated side effects; thus, there is need for alternative means of managing this life-threatening disease. These drugs do not achieve the recommended blood pressure target in most people; more so majority of people with hypertension do not follow the treatment regimen religiously. Some Africans have been reported to become normotensive as a result of dietary consumption of spices. Several spices have been used over the years in Africa to manage hypertension. The aim of this review is to evaluate the ethnomedicinal use, bioactive phytochemical composition, bioactive compounds present, and pharmacological applications of spices commonly used in Africa for managing hypertension. Most of the plants used contained polyphenols, flavonoids, tannins, anthraquinone, flavonoids, cardiac glycosides, and saponins. Dietary supplementation of Xylopia aethiopica and other spices in diet have been proven to significantly reduced plasma angiotensin-I-converting enzyme (ACE) than simvastatin (the reference drug). Toxicological, histological, and hematological evaluation revealed that acute and chronic consumption of most of these spices are safe. Studies have also revealed that some of the spices can be used as alternative therapy alongside usual antihypertensive medications. PRACTICAL IMPLICATION: The prevalent rate of hypertension is on the increase in both the developed and developing countries. People often skip medication due to their busy schedule and anti-hypertensive potential side effects; however, this is not the case with food/spices as most people consumed them daily. Deliberate, right combinations and consistent incorporation of spices with proven anti-hypertensive potential into our diet may be of great benefit in normalizing blood pressure and mitigate other complications on the heart and vital organs.

Mismatch Repair Protein Expressions in Cohort of Colorectal Carcinoma Patients in Lagos.

BACKGROUND: Colorectal carcinoma (CRC) is a major cause of morbidity and mortality worldwide. Microsatellite instability pathway is important in the pathogenesis of CRC. Immunohistochemistry expression of mismatch repair (MMR) proteins serves as surrogate marker for MMR gene mutation. AIMS: This study aimed to determine MSI status of a cohort of CRC cases using immunohistochemistry. MATERIALS AND METHOD: Surgical pathology blocks of resected colonic carcinoma (CC) between 2011 and 2015 were extracted from our departmental archives and The Specialist Laboratories in Lagos. Immunohistochemical expression profile of 4 MMR proteins was assessed in the representative blocks and this was correlated with the demographic and pathological characteristics. RESULTS: There were 19 males and 16 females with CC, mean age of 51.6 years, and 40% of them were below 50 years of age. Twenty (57.1%) out of the 35 CC cases seen were mismatch repair proficient (pMMR) while the remaining 15 (42.9%) were mismatch repair deficient (dMMR). Seven dMMR cases were seen equally on the right and left colonic tumors respectively. Five (71.4%) out of the 7 mucinous tumors in this study were dMMR, right sided with 3 of them in patients who were below 50 years of age. CONCLUSION: The frequency of mismatch repair deficiency in CC among Nigerians is high, and presence of right-sided mucinous colon cancer in patients below 50 years is highly suggestive of dMMR status. Mutation studies of larger patient samples to determine the percentage with germline mutation will further our knowledge, and influence therapeutic options for CC.

Surgical consent during the COVID-19 pandemic.

BACKGROUND AND AIMS: During the COVID-19 pandemic, surgical practice may deviate with operative and non-operative management considered. Appropriate discussion of options with patients is paramount to quality surgical care. Intercollegiate and EAES guidelines recommend discussing and documenting risk of COVID-19 exposure in the consent process for patients undergoing surgery. MATERIALS AND METHODS: Closed-loop audit of consent forms for patients undergoing emergency and elective surgical procedures. Interventions implemented included education of wider surgical teams. Data was collected during a one-week period for each cycle and analysed using Chi-squared test. RESULTS: In cycle 1, 6/17 (35.3%) case notes documented discussion of COVID-19 risk. Following intervention, compliance improved to 23/29 (79.3%) cases in cycle 2 and 33/45 (73.3%) cases in cycle 3. CONCLUSION: Pre-intervention, our consenting practice was non-compliant. Our interventions led to significant and sustained improvements in practice. We recommend provision of wider surgical team education to facilitate good consenting practice.

Dietary vitamin D ameliorates hepatic oxidative stress and inflammatory effects of diethylnitrosamine in rats.

The generation of reactive oxygen species (ROS) plays an essential role in the pathogenesis of several diseases. Its implication in inflammation has suggested a possible link between oxidative stress and activation/release of cytokines in precancerous states. Recent observational studies have suggested an association between inflammation and vitamin D deficiency; hence, suggesting that vitamin D could play a role in the pathogenesis of diseases. This study examined the antioxidant and anti-inflammatory potentials of vitamin D in diethylnitrosamine (DEN)-induced oxidative stress and inflammation in rats. Rats were divided into four experimental groups. While groups one and two were administered twice weekly with 30 mg/kg body weight DEN for six weeks, groups three and four were given normal saline. Groups one and three were fed with vitamin D deficient diet, while groups two and four were fed vitamin D diet during the experiment. After that, biomarkers of oxidative stress status were assayed spectrophotometrically. The concentration of inflammatory cytokines was determined using enzyme-linked immunosorbent assay (ELISA). DEN-induced vitamin D deficient diet group had increased antioxidant enzymes' activities. Also, there were elevated concentrations of thiobarbituric acid reactive substances (TBARS) and inflammatory cytokines in the same group. Vitamin D diet, however, reduced oxidative stress effects through the reduction in the activities of TBARS and caused a significant (p < 0.05) increase in nitric oxide concentration. Vitamin D diet significantly (p < 0.05) reduced the level of interleukin 1ß and TNF-α produced in the deficiency state. These findings show that vitamin D may play an essential role in the regulation of hepatic oxidative stress and inflammatory responses.

Latex glove conduit as improvised blood vessel model for microvascular anastomosis training.

BACKGROUND: In the growing need of microvascular surgery in modern-day plastic surgery, financial burden on surgeon or institution can discourage acquisition of skill particularly in the initial phase of laboratory simulation. This article describes the construction of a cheap, easy-to-make blood vessel model. MATERIALS AND METHOD: The model was made using infusion giving set, latex glove, scissors, tape measure and Swan glue CD 308. A cut sheet from the latex glove was rolled twice over two glue-painted segment of the infusion giving set stent. The stents were gently pulled out, turning the sheet into a conduit. The blood vessel model was then allowed to dry. DISCUSSION: The use of latex glove for initial training in microvascular anastomosis has been for long. Previously described productions into a conduit are cumbersome. This model is easy to construct and is useful in an office or dry laboratory setting. CONCLUSION: The latex glove blood vessel model described in this article is a useful material in the training of budding microsurgeons. Residents in our institution have reported a very good learning experience with its use.

Kinetics of angiotensin -1 converting enzyme inhibition and antioxidative properties of Azadirachta indica seed protein hydrolysates.

Neem (Azadirachta indica) seed protein hydrolysates were investigated for in vitro antioxidant and angiotensin 1-converting enzyme (ACE)-inhibitory activities. Neem seed proteins were hydrolysed using pepsin, trypsin and Alcalase. The degree of pepsin hydrolysis of neem seed protein was significantly higher (p < 0.05) than those of trypsin and Alcalase hydrolysis. Proteolytic hydrolysis of the isolate resulted in hydrolysates with improved Arg/Lys ratio, with pepsin hydrolysates still being able to maintain an acceptable level of essential amino acids comparable to that of the isolate. At 2.5 mg/mL, pepsin neem seed protein hydrolysate (NSPH) demonstrated the strongest antioxidant activity with 67.15 % and 50.07 % DPPH- and superoxide anion radical-scavenging activities, respectively, while trypsin NSPH had the highest ferric-reducing power. Using N-[3-(2-furyl)acryloyl]-L-phenylalanyl-glycyl-glycine (FAPGG) as substrate, NSPHs strongly inhibited ACE (69.20-80.39 %) in a concentration-dependent manner. Pepsin NSPH had higher ACE-inhibitory activity than trypsin and Alcalase NSPHs. Kinetic studies showed the mechanism of ACE inhibition to be mixed-type with Ki values of 0.62, 0.84, 1.5 for pepsin, trypsin and alcalase NSPH, respectively. These results suggest that NSPH can be used as a potential nutraceutical with antioxidant capacity and inhibitory activity against ACE.

Immunohistochemical Analysis of BRAF (V600E) Mutation and P16 Expression in Malignant Melanoma in Lagos, Nigeria: A 10-Year Retrospective Study.

BACKGROUND: In Blacks, malignant melanoma (MM) is associated with greater morbidity and mortality compared to Caucasians. MMs with BRAF V600E mutation as well as those with loss of p16 protein expression are associated with aggressive behavior and worse prognosis. OBJECTIVES: We determined BRAF (V600E) mutation status and loss of p16 expression in MM cases in Lagos, Nigeria, and correlated these with histopathologic parameters and patients' age. METHODS: Forty-five cases of MM received between January 2005 and December 2014 in the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital were subjected to immunohistochemical studies to determine BRAF V600E mutation and p16 protein expression. These included cutaneous (n=37), musosal (n=3), and ocular MM (n=2) as well as lymph node metastatases (n=3). RESULTS: BRAF (V600E) mutations were detected in 5/45 (11%) while 31/45 (69%) of the cases had loss of p16 expression. No statistically significant association was found between the BRAF (V600E) mutation, loss of p16 expression, and histologic parameters such as histologic variant, Clark level, Breslow thickness, and ulceration. CONCLUSION: BRAF (V600E) mutation was detected only in a small proportion of cases while loss of p16 expression occurred in most cases which also had high Clark level, high Breslow thickness, and ulceration.

The use of special stains in liver biopsy interpretation: Implications for the management of liver disease in Nigeria.

CONTEXT: The evaluation of a liver biopsy requires the use of stains other than routine hematoxylin and eosin (H and E) to highlight many important features. AIMS: Most Nigerian Histopathology Departments do not routinely perform special stains (personal communication by authors). This study aims to re-evaluate a set of liver biopsies which has been diagnosed solely on H and E stains by performing a standard set of special stains on them. SETTINGS AND DESIGN: This is a retrospective analysis. MATERIALS AND METHODS: The formalin fixed paraffin embedded blocks of liver biopsies reported in two histopathology laboratories between 2008 and 2013 were retrieved. These were stained with H and E and the following standard special stains for liver tissue histology - Perl's Prussian blue, reticulin, Sirius red, Shikata orcein, and periodic acid-Schiff with diastase. The stained slides were re-analyzed. STATISTICAL ANALYSIS USED: No formal statistical analysis was performed, but results are summarized and tabulated by summary statistics, where appropriate. RESULTS: Seventy-four liver biopsy paraffin blocks were received in the laboratories. Fifty-three (71.6%) were suitable for analysis out of which 51 (68.9%) had their clinical details retrievable. In 29 cases (56.9%), Perl's stain was positive for iron pigment within the hepatocytes with 17 (58.6%) of these being Grade 1, 7 (24.1%) Grade 2, and 5 (17.2%) Grade 3. Shikata orcein revealed hepatitis B viral surface antigen in 15 (29.4%) of the cases while copper-associated protein was demonstrable in 6 (11.8%) of the cases. The discovery of stainable iron implies some degree of disturbance of iron metabolism, and a Grade 3 stainable iron requires investigation for genetic hemochromatosis. The demonstration of copper-associated proteins suggests biliary disease in a noncirrhotic liver which also requires further investigation. CONCLUSION: This study confirms the need to routinely perform special stains in reporting liver biopsies to fully investigate and manage patients and their relatives.

Histopathology practice and training in Nigeria ­ a model.

Objectives: Contemporary histopathology practice and training in Nigeria have been plagued by the fundamental issue of inadequate exposure to surgical pathology material by both trainees and trainers. This paper critically examines the factors that affect the discipline and profers practical solutions to aid its advancement. Materials and Method: This review is based on the authors experience and observations of histopathology practice in Nigeria. Results: The Nigerian health sector is plagued by many ills including poor funding, weak policies, dilapidated structures, disgruntled and frustrated practitioners, amongst others - and pathologists are not immune to all these. In recent times, there has been a proliferation of accredited training centres as well as medical graduates interested in the specialty of histopathology. The busiest histopathology laboratories in the country ascession between 2200 and 5500 surgical samples yearly. Thus there is inadequate exposure by histopathologists and trainee pathologists to surgical materials with the attendant consequences. Many centres still rely principally on routine haematoxylineosin stains. There are no nationally agreed standard reporting formats for most diseases. Conclusion: The development of a deanery or regional system of accredited histopathology laboratories may form the fulcrum for improving the overall quality of histopathological services and training in Nigeria. This will help develop local expertise and ensure adequate exposure to teaching aids and surgical materials. We hope that the proffered solutions will help encourage local pathologists to continue and increase their efforts to raise the profession up to enviable heights.

Preoperative assessment of retrorectal tumours.

BACKGROUND: Retrorectal tumours present diagnostic and surgical challenges. This study aimed to identify whether preoperative imaging and/or biopsy provide diagnostic accuracy. METHODS: A consecutive series of patients who had undergone excision of a retrorectal tumour were identified from a database (2002-2013). Details of patient demographics, preoperative presentation, imaging, biopsy, surgical procedure, and gross and microscopic pathology were reviewed. Preoperative imaging and/or biopsies were compared with eventual pathology findings. RESULTS: In total, 76 patients were identified, all of whom had undergone preoperative cross-sectional imaging whereas only 22 had preoperative biopsy. Imaging correctly discriminated benign from malignant tumours in 72 of the 76 patients (specificity 97 per cent, sensitivity 88 per cent, positive predictive value 88 per cent and negative predictive value 97 per cent). The corresponding values for preoperative biopsy (benign versus malignant) were 100, 83, 100 and 93 per cent. None of the four patients who were assessed incorrectly as having benign or malignant disease on imaging would have undergone an alternative procedure had this been known before surgery. Preoperative biopsy did not significantly influence patient management, and the absence of preoperative biopsy had no detrimental effect; a definitive preoperative histological diagnosis would not have influenced subsequent management. CONCLUSION: Preoperative imaging was accurate in the assessment of retrorectal tumours, whereas biopsy did not add to the surgical strategy.

ß1a490-508, a 19-residue peptide from C-terminal tail of Cav1.1 ß1a subunit, potentiates voltage-dependent calcium release in adult skeletal muscle fibers.

The α1 and ß1a subunits of the skeletal muscle calcium channel, Cav1.1, as well as the Ca(2+) release channel, ryanodine receptor (RyR1), are essential for excitation-contraction coupling. RyR1 channel activity is modulated by the ß1a subunit and this effect can be mimicked by a peptide (ß1a490-524) corresponding to the 35-residue C-terminal tail of the ß1a subunit. Protein-protein interaction assays confirmed a high-affinity interaction between the C-terminal tail of the ß1a and RyR1. Based on previous results using overlapping peptides tested on isolated RyR1, we hypothesized that a 19-amino-acid residue peptide (ß1a490-508) is sufficient to reproduce activating effects of ß1a490-524. Here we examined the effects of ß1a490-508 on Ca(2+) release and Ca(2+) currents in adult skeletal muscle fibers subjected to voltage-clamp and on RyR1 channel activity after incorporating sarcoplasmic reticulum vesicles into lipid bilayers. ß1a490-508 (25 nM) increased the peak Ca(2+) release flux by 49% in muscle fibers. Considerably fewer activating effects were observed using 6.25, 100, and 400 nM of ß1a490-508 in fibers. ß1a490-508 also increased RyR1 channel activity in bilayers and Cav1.1 currents in fibers. A scrambled form of ß1a490-508 peptide was used as negative control and produced negligible effects on Ca(2+) release flux and RyR1 activity. Our results show that the ß1a490-508 peptide contains molecular components sufficient to modulate excitation-contraction coupling in adult muscle fibers.

A major facilitator superfamily protein participates in the reddish brown pigmentation in Bombyx mori.

MucK is a member of the major facilitator super family (MFS) and is within a subgroup involved in the uptake of organic acids. Here, we provide the first evidence that mucK is required for normal body color pattern in insect larvae. In the cts mutant strain of Bombyx mori (Linnaeus), the larval anal plates, prothoracic tergum, and the head are reddish brown, as opposed to the white color found in the wild type. Positional cloning of the cts gene was carried out and it was mapped within 90kb on the 16th chromosome. Two molecular markers, 182A4 and 242GA, were found co-segregated with the cts phenotype. Only one candidate gene in the region, BGIBMGA013242, which codes for a major facilitator super family protein named BmMucK, located between the two loci. Sequence analysis revealed that a ∼3kb deletion in the genome resulting in a 126bp deletion in the open reading frame (ORF) of BmmucK in the cts mutant. Fluorescence in situ hybridization (FISH) and quantitative reverse transcription PCR showed that BmmucK expression coincided with reddish brown pigmented regions in the cts mutant strain. BmmucK expression in the head and anal plates were markedly elevated at the molting stages. We performed RNA interference of the mucK homolog in Tribolium castaneum and observed brown coloration accompanied by lethality in ∼1/3 of the insects. The results suggest that MucK plays an important role in the pigmentation process of insect larvae.

Effects of fibre-enriched diets on tissue lipid profiles of MSG obese rats.

In order to investigate the influence of some fibre-enriched diets on tissue lipids in an animal model of obesity induced by the administration of monosodium glutamate (MSG), obese rats were fed diets containing 30% of Acha, Cassava, Maize and Plantain for five weeks and weight gain, feed intake and lee index were recorded. The lipid profiles of plasma, erythrocytes, kidney, heart and liver as well as hepatic 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase activity were measured. The diets significantly (p<0.05) reduced weight gain and lee index in the obese rats. Obesity-induced increase in plasma and erythrocytes lipid levels was significantly (p<0.05) reduced by these diets. MSG-induced obesity also resulted in a significant increase (p<0.05) in hepatic cholesterol level which was reduced by the diets. MSG-obesity was characterised by a significant (p<0.05) increase in cholesterol, triacylglycerol and phospholipids in kidney and this was reversed by the diets except Maize which did not reverse the increased cholesterol level. Only Acha reversed the obesity-induced increase in heart cholesterol and phospholipids. The increased activity of hepatic HMG-CoA reductase associated with obesity was also significantly (p<0.05) reduced by the diets. In conclusion, dyslipidemia associated with MSG-induced obesity could be attenuated by consumption of fibre-enriched diets.

KRAS and BRAF mutations in Nigerian colorectal cancers.

PURPOSE: Activation of the KRAS oncogene is implicated in colorectal carcinogenesis and mutations have been reported in 30-50% of cases. BRAF mutation, though less common, is also reported and importantly associated with shorter progression-free interval. This study aims to determine the KRAS and BRAF mutation statuses of Nigerian colorectal cancers (CRC). METHODS: Mutation analysis was carried out on archival paraffin-embedded blocks of CRC tissues. KRAS codons 12, 13 and 61 and BRAF V600E were assessed by pyrosequencing after DNA extraction from 200 cases at the Leeds Institute of Molecular Medicine, St. James's University Hospital, UK. Mutation rates and the spectra were determined. RESULTS: Pyrosequencing was successful in 112 of 200 cases. KRAS mutation in codons 12 and 13 was demonstrated in 23 of 112 cases (21%); none in codon 61. BRAF mutation in codon 600 was demonstrated in 4.5%. CONCLUSION: This study shows that 21% of Nigerian CRC patients carry a KRAS mutation; half the rate in Caucasians; and that BRAF mutation also occurs in Nigerian CRC cancers.

Mice null for calsequestrin 1 exhibit deficits in functional performance and sarcoplasmic reticulum calcium handling.

In skeletal muscle, the release of calcium (Ca(2+)) by ryanodine sensitive sarcoplasmic reticulum (SR) Ca(2+) release channels (i.e., ryanodine receptors; RyR1s) is the primary determinant of contractile filament activation. Much attention has been focused on calsequestrin (CASQ1) and its role in SR Ca(2+) buffering as well as its potential for modulating RyR1, the L-type Ca(2+) channel (dihydropyridine receptor, DHPR) and other sarcolemmal channels through sensing luminal [Ca(2+)]. The genetic ablation of CASQ1 expression results in significant alterations in SR Ca(2+) content and SR Ca(2+) release especially during prolonged activation. While these findings predict a significant loss-of-function phenotype in vivo, little information on functional status of CASQ1 null mice is available. We examined fast muscle in vivo and in vitro and identified significant deficits in functional performance that indicate an inability to sustain contractile activation. In single CASQ1 null skeletal myofibers we demonstrate a decrease in voltage dependent RyR Ca(2+) release with single action potentials and a collapse of the Ca(2+) release with repetitive trains. Under voltage clamp, SR Ca(2+) release flux and total SR Ca(2+) release are significantly reduced in CASQ1 null myofibers. The decrease in peak Ca(2+) release flux appears to be solely due to elimination of the slowly decaying component of SR Ca(2+) release, whereas the rapidly decaying component of SR Ca(2+) release is not altered in either amplitude or time course in CASQ1 null fibers. Finally, intra-SR [Ca(2+)] during ligand and voltage activation of RyR1 revealed a significant decrease in the SR[Ca(2+)](free) in intact CASQ1 null fibers and a increase in the release and uptake kinetics consistent with a depletion of intra-SR Ca(2+) buffering capacity. Taken together we have revealed that the genetic ablation of CASQ1 expression results in significant functional deficits consistent with a decrease in the slowly decaying component of SR Ca(2+) release.