Molecular insights into Pashmina fiber production: comparative skin transcriptomic analysis of Changthangi goats and sheep.

Ladakh, one of the highest inhabited regions globally, hosts the unique Changthangi goat, renowned for producing Pashmina, the world's most luxurious natural fiber. In comparison, the fiber derived from Changthangi sheep is considered next only to Pashmina. This research endeavors to compare the skin transcriptome profiles of Changthangi goats and Changthangi sheep, aiming to discern the molecular determinants behind the recognition of Changthangi goats as the source of Pashmina. Drawing upon previously conducted studies, a collective of 225 genes correlated with fiber characteristics were extracted from the differentially expressed genes noticed between the two species (p-value of ≤ 0.05 and a log2 fold change of ≥ 1.5). These genes were analyzed using DAVID software to understand their biological functions and to identify enriched KEGG and Reactome pathways. The protein-protein interaction networks were constructed using Cytoscape, cytoHubba, and STRING to focus on key genes and infer their biological significance. Comparative transcriptome analysis revealed significantly higher expression of genes involved in signaling pathways like Wnt, MAPK, PI3K-Akt, Hedgehog, associated with fiber development and quality in Changthangi goats. These pathways play crucial roles in hair follicle (HF) formation, maintenance of epidermal stem cells, and fiber characteristics. Findings also highlight the enrichment of cell adhesion molecules and ECM-receptor interaction, emphasizing their roles in HF structure, growth, and signaling. This investigation offers an in-depth understanding of the molecular intricacies governing Pashmina production in Changthangi goats, providing valuable insights into their unique genetic makeup and underlying mechanisms influencing the exceptional quality of Pashmina fibers.

Comprehensive evaluation and validation of optimal reference genes for normalization of qPCR data in different caprine tissues.

BACKGROUND: Quantitative real-time PCR (qPCR) is a highly reliable method for validating gene expression data in molecular studies due to its sensitivity, specificity, and efficiency. To ensure accurate qPCR results, it's essential to normalize the expression data using stable reference genes. METHODS: This study aimed to identify suitable reference genes for qPCR studies in goats by evaluating 18 candidate reference genes (ACTB, BACH1, B2M, GAPDH, HMBS, HPRT1, PGK1, PPIA, PPIB, RPLP0, RPL19, RPS9, RPS15, RPS28, SDHA, TBP, UXT, and YWHAZ) in 10 different caprine tissues (heart, intestine, kidney, liver, lung, muscle, rumen, skin, spleen, and testis). An integrated tool called RefFinder, which incorporates various algorithms like NormFinder, GeNorm, BestKeeper, and ΔCt, was used to assess the stability of expression among these genes. RESULTS: After thorough analysis, ACTB, PPIB, and B2M emerged as the most stable reference genes, while RPL19, RPS15, and RPS9 were found to be the least stable. The suitability of the selected internal control genes was further validated through target gene analysis, confirming their efficacy in ensuring accurate gene expression profiling in goats. CONCLUSION: The study determined that the geometric average of ACTB, PPIB, and B2M creates an appropriate normalization factor for gene expression studies in goat tissues.

Potential of carboxymethyl cellulose coating and low dose gamma irradiation to maintain storage quality, inhibit fungal growth and extend shelf-life of cherry fruit.

Carboxymethyl cellulose (CMC) coatings alone and in combination with gamma irradiation was tested for maintaining the storage quality, inhibiting fungal incidence and extending shelf-life of cherry fruit. Two commercial cherry varieties viz. Misri and Double after harvest at commercial maturity were coated with CMC at levels 0.5-1.0 % w/v and gamma irradiated at 1.2 kGy. The treated fruit including control was stored under ambient (temperature 25 ± 2 °C, RH 70 %) and refrigerated (temperature 3 ± 1 °C, RH 80 %) conditions for evaluation of various physico-chemical parameters. Fruits were evaluated after every 3 and 7 days under ambient and refrigerated conditions. CMC coating alone at levels 0.5 and 0.75 % w/v was not found effective with respect to mold growth inhibition under either of the two conditions. Individual treatment of CMC coating at 1.0 % w/v and 1.2 kGy irradiation proved helpful in delaying the onset of mold growth up to 5 and 8 days of ambient storage. During post-refrigerated storage at 25 ± 2 °C, RH 70 %, irradiation alone at 1.2 kGy gave further 4 days extension in shelf-life of cherry varieties following 28 days of refrigeration. All combinatory treatments of CMC coating and irradiation proved beneficial in maintaining the storage quality as well as delaying the decaying of cherry fruit during post-refrigerated storage at 25 ± 2 °C, RH 70 % but, combination of CMC at 1.0 % w/v and 1.2 kGy irradiation was found significantly (p ≤ 0.05) superior to all other treatments in maintaining the storage quality and delaying the decaying of cherry fruit. The above combinatory treatment besides maintaining storage quality resulted in extension of 6 days in shelf life of cherry varieties during post-refrigerated storage at 25 ± 2 °C, RH 80 % following 28 days of refrigeration. Above Combination treatment gave a maximum of 2.3 and 1.5 log reduction in yeast and mold count of cherry fruits after 9 and 28 days of ambient and refrigerated storage, thereby ensuring consumer safety.

Identification and validation of stable reference genes for expression profiling of target genes in diverse ovine tissues.

Quantitative PCR (qPCR) is a widely-used technique for quantifying the expression of target genes across various tissues, as well as under different pathological and physiological conditions. One of the challenges associated with this method is the need to identify optimal reference genes (RGs) that maintain consistent expression levels under diverse experimental settings, thereby ensuring accurate biological interpretation. In this study, we conducted a thorough analysis of 18 candidate RGs (ACTB, BACH1, B2M, GAPDH, HMBS, HPRT1, PGK1, PPIA, PPIB, RPLP0, RPL19, RPS9, RPS15, RPS28, SDHA, TBP, UXT, and YWHAZ) across 10 ovine tissues (muscle, skin, kidney, liver, intestine, rumen, lung, testis, heart, and spleen) obtained from five individual sheep. We aimed to identify genes with stable expression across these tissues. A literature-based survey helped us shortlist candidate genes representing various functional classes from multiple livestock species. We employed four algorithms: geNorm, NormFinder, BestKeeper, and Delta Ct (ΔCt), to rank these genes based on their stability. A consistent trend in the rankings was observed across these different algorithms. RefFinder was then used for a comprehensive ranking, integrating the outputs from the various methods. ACTB, PPIB, BACH1, and B2M emerged as the most stable RGs, while RPS9, RPS15, and PGK1 displayed variable expression. We validated our findings through qPCR analysis of four target genes (ACTN2, CRYAB, DLK1, and TRIM54) in the skin samples from two different sheep breeds. Based on these results, we recommend ACTB, PPIB, BACH1, and B2M as reliable internal control genes for qPCR experiments involving diverse ovine tissues.

Diarrhoeagenic Escherichia coli and salmonellae in calves and lambs in Kashmir absence, prevalence and antibiogram.

Polymerase chain reaction assays and culture were used to investigate 728 faecal samples from 404 calves (286 diarrhoeic, 118 healthy) and 324 lambs (230 diarrhoeic, 94 healthy) in Kashmir, India, for the presence of enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli (EAEC), diffusely adherent E. coli (DAEC) and salmonellae. Antimicrobial sensitivity patterns were also investigated. In total, 23 ETEC isolates were obtained from the diarrhoeic calves and 12 from diarrhoeic lambs. Most (74%) of the isolates from calves harboured the gene encoding heat-labile enterotoxin I, whereas 75% of the isolates from lambs possessed only the gene encoding for heat-stable enterotoxin a. The ETEC isolates belonged to 20 serogroups, among which serogroups O15 (five isolates) and O8 (four isolates) were the most frequent. Salmonella Typhimurium or S. Enteritidis was identified in three samples from diarrhoeic lambs. The ETEC isolates and the salmonellae showed multidrug resistance. No EAEC or DAEC was detected in any of the samples.

Genome-wide characterization and development of SSR markers for genetic diversity analysis in northwestern Himalayas Walnut (Juglans regia L.).

In the present study, we designed and validated genome-wide polymorphic SSR markers (110 SSRs) by mining the walnut genome. A total of 198,924 SSR loci were identified. Among these, successful primers were designed for 162,594 (81.73%) SSR loci. Dinucleotides were the most predominant accounting for 88.40% (175,075) of total SSRs. The SSR frequency was 377.312 SSR/Mb and it showed a decreasing trend from dinucleotide to octanucleotide motifs. We identified 20 highly polymorphic SSR markers and used them to genotype 72 walnut accessions. Over all, we obtained 118 alleles that ranged from 2 to 12 with an average value of 5.9. The higher SSR PIC values indicate their robustness in discriminating walnut genotypes. Heat map, PCA, and population structure categorized 72 walnut genotypes into 2 distinct clusters. The genetic variation within population was higher than among population as inferred by analysis of molecular variance (AMOVA). For walnut improvement, it is necessary to have a large repository of SSRs with high discriminative power. The present study reports 150,000 SSRs, which is the largest SSR repository for this important nut crop. Scientific communities may use this repository for walnut improvement such as QTL mapping, genetic studies, linkage map construction, and marker-assisted selection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03563-6.

Storage of cellular 5' mRNA caps in P bodies for viral cap-snatching.

The minus strand and ambisense segmented RNA viruses include multiple important human pathogens and are divided into three families, the Orthomyxoviridae, the Bunyaviridae, and the Arenaviridae. These viruses all initiate viral transcription through the process of "cap-snatching," which involves the acquisition of capped 5' oligonucleotides from cellular mRNA. Hantaviruses are emerging pathogenic viruses of the Bunyaviridae family that replicate in the cytoplasm of infected cells. Cellular mRNAs can be actively translated in polysomes or physically sequestered in cytoplasmic processing bodies (P bodies) where they are degraded or stored for subsequent translation. Here we show that the hantavirus nucleocapsid protein binds with high affinity to the 5' cap of cellular mRNAs, protecting the 5' cap from degradation. We also show that the hantavirus nucleocapsid protein accumulates in P bodies, where it sequesters protected 5' caps. P bodies then serve as a pool of primers during the initiation of viral mRNA synthesis by the viral polymerase. We propose that minus strand segmented viruses replicating in the cytoplasm have co-opted the normal degradation machinery of P bodies for storage of cellular caps. Our data also indicate that modification of the cap-snatching model is warranted to include a role for the nucleocapsid protein in cap acquisition and storage.

Isolation of atypical enteropathogenic Escherichia coli and Shiga toxin 1 and 2f-producing Escherichia coli from avian species in India.

AIMS: To study the prevalence and characterize atypical enteropathogenic Escherichia coli (EPEC) and Shiga toxin producing E. coli (STEC) in avian species in India. METHODS AND RESULTS: Two hundred and twelve faecal samples collected from 62 chickens, 50 ducks and 100 pigeons were investigated for the presence of stx(1), stx(2), eae and ehxA virulence genes by multiplex PCR. In all, 42 E. coli isolates (25 chicken, 2 duck and 15 pigeon) possessed at least one virulence gene. Out of these, nine (4.24%) isolates were STEC and 33 (15.56%) were EPEC. All isolates from duck and chicken were EPEC while among 15 pigeon isolates nine (60%) were STEC and six (40%) were EPEC. Among the STEC isolates four each carried stx(1) or stx(2) and one possessed both stx(1) and stx(2). Subtype analysis of stx revealed the presence of stx(2f) in four STEC isolates. None of the STEC isolates carried stx(1c), stx(2c), stx(2d) or stx(2e). Isolates carrying stx(2f) demonstrated vero cell toxicity. One each belonged to serogroup O17 and O78, while one was rough and the other untypeable. All EPEC isolates were atypical as they lacked bfpA. This appears to be the first report of detection of stx(2f) from India. CONCLUSIONS: The study established the presence of stx(1) and stx(2f) containing E. coli in pigeons and atypical EPEC in poultry in India. Pigeons might serve as vectors for transmission of STEC to environment and humans. SIGNIFICANCE AND IMPACT OF THE STUDY: Taking into account the close contact between fanciers and pigeons, these findings warrant a more critical appraisal of these zoonotic pathogens in pigeons and humans.

Mycophenolate mofetil in the treatment of retroperitoneal fibrosis.

The pathogenesis of idiopathic retroperitoneal fibrosis (IRPF) has been attributed to an autoimmune response to atherosclerotic lipid material leaking from blood vessels. Corticosteroids and cytotoxic agents have been used for therapy. Based on the immunosuppressive and anti-fibrotic action of mycophenolate, we administered this agent to a patient with biopsy-proven IRPF and achieved a rapid, complete and sustained remission with a 6-year follow-up.

Isolation of a sodium transport inhibitory factor, inhibitin, from cultured leukemic promyelocytes.

Previous studies have shown that leukemic blood contains a factor that has an inhibitory effect on bidirectional sodium transport in erythrocytes. This study was designed to isolate this factor from cultured leukemic promyelocytes. An extract from the promyelocytes reduced significantly (P less than 0.001) the ouabain-insensitive sodium efflux rate, from 0.096 +/- 0.009 to 0.056 +/- 0.003 SD. Using the inhibition of ouabain-insensitive sodium transport in erythrocytes as an assay to identify the factor, we ran the crude promyelocyte extract through Sephadex G-25 and G-10, with an intermediate ion-exchange step on DE-32, and finally subjected the active fraction to reverse-phase high-performance liquid chromatography. The specific inhibitory activity of the final fraction was 180-fold higher than that of the crude promyelocyte extract. The inhibitory activity could be destroyed by acid hydrolysis and by enzymatic digestion with several proteases but not by heating at 80 degrees C for 30 min; these characteristics suggest that the active factor, called inhibitin, is a peptide. Inhibitin is released by immature myeloid cells but not by differentiated white cells or by leukemic lymphocytes. It has no effect on potassium influx but inhibits sodium/sodium exchange in erythrocytes.

Inhibitin: a specific inhibitor of sodium/sodium exchange in erythrocytes.

An inhibitor of ouabain-insensitive sodium/sodium exchange in erythrocytes has been isolated from leukemic promyelocytes. To explore the specific effects of this inhibitor, named inhibitin, sodium transport experiments were carried out in human erythrocytes. Inhibitin reduced ouabain-insensitive bidirectional sodium transport. It did not change net sodium fluxes, had no significant effect on rubidium influx, and did not inhibit sodium-potassium-ATPase activity. The inhibitory effect of inhibitin was studied on sodium/sodium exchange and on sodium/lithium countertransport in 140 mM sodium and in sodium-free media. In the presence of sodium, inhibitin reduced sodium and lithium efflux to that observed in sodium-free medium. Inhibitin showed no reduction in sodium or lithium efflux when sodium was replaced by choline chloride or Mg2+. When inhibitin was combined with one or more of the other transport inhibitors (i.e., ouabain, furosemide, or bumetanide and amiloride), its inhibitable component remained distinct and it did not overlap with that of the other inhibitors. These studies show that inhibitin is a specific inhibitor of carrier-mediated sodium/sodium exchange and sodium/lithium countertransport processes in human erythrocytes.

Release of a sodium transport inhibitor (inhibitin) from cultured human cancer cells.

In this study we investigated whether the sodium transport inhibitor, inhibitin, originally isolated from leukemic promyelocytes, was also elaborated by some other neoplastic cells in culture. Like culture medium from the leukemic promyelocytes (HL60), the media from two other leukemic cell lines (erythroblasts K562 and monoblasts U937) also showed significant inhibitory activity on ouabain-insensitive sodium efflux rate constant in normal erythrocytes. Similarly, culture media from three neoplastic cell lines (H.Ep2, MRC5, and HX99) also showed significant inhibitin-like inhibitory activity. Using high-performance liquid chromatography to isolate inhibitin, culture media from HL60 and H.Ep2 cells were identically treated, and inhibitin isolated from H.Ep2 cells had the same retention time as that shown by promyelocyte inhibitin. H.Ep2 inhibitin reduced ouabain- and bumetanide-insensitive sodium efflux rate constant from 0.1510 +/- 0.0275 (SD) to 0.0988 +/- 0.0110 (P less than 0.005). Like promyelocyte inhibitin, H.Ep2 inhibitin reduced sodium efflux and influx by equivalent amounts suggesting thereby that it is a sodium/sodium exchange inhibitor. These studies show that a factor exhibiting inhibitory activity on sodium/sodium exchange is secreted by a variety of leukemic and neoplastic cells in culture.

Interaction of inhibitin with the human erythrocyte Na+(Li+)i/Nao+ exchanger.

The kinetic interactions of inhibitin, a peptide isolated from cultured leukaemic promyelocytes, with erythrocyte Na+/Na+ and Na+/Li+ exchanges have been investigated. Inhibitin (1 microM) reduced the ouabain- and bumetanide-resistant sodium efflux and influx by equivalent amounts indicating an inhibitin-sensitive exchange component of 0.52 mmol/l per h. This value was not significantly different from that measured as the difference in sodium-rich (140 mM) and sodium-free media (0.49 mmol/l per h). Similarly, the inhibitin-sensitive lithium efflux was equivalent to the sodium/lithium countertransport component (0.36 vs. 0.34 mmol/l per h), indicating that both exchanges were mediated by the same transport process, which is inhibitin-sensitive. The dose-response curve revealed the presence of a single inhibitin binding site per exchanger with a Ki of 2.10(-7) M. In kinetic inhibition studies, inhibitin (0.1 microM) decreased the Vmax of ouabain- and bumetanide-resistant sodium efflux with no effect on the Km for external sodium, i.e., inhibitin displayed a non-competitive mechanism of action. These findings indicate that inhibitin interacts with the Na+(Li+)i/Nao+ exchanger at a site distinct from the sodium binding site.

Identifying factors affecting age at first semen freezing and age at first semen use in Sahiwal bulls.

AIM: The objective of the study was to evaluate the effects of non-genetic factors on reproduction traits viz. age at first semen freezing and age at first semen use of breeding bulls in Sahiwal bulls by fitting least-squares analysis. MATERIALS AND METHODS: The information on reproduction traits of 43 Sahiwal breeding bulls belonging to 8 sets of Sahiwal breeding program at Indian Council of Agricultural Research-National Dairy Research Institute (ICAR-NDRI), Karnal (Haryana), India during 27 years (1987-2013) were analyzed using fixed linear model. The information was collected from AI records, reproduction sheets, and bull AI register maintained at different sections of Institute viz. record room of Dairy Cattle Breeding Division (DCB), Cattle Yard, Artificial Breeding Research Centre, ICAR-NDRI, Karnal. RESULTS: The average age at first semen freezing and age at first semen use of Sahiwal breeding bulls was estimated as 3.17±0.01 years and 5.35±0.01 years, with the coefficient of variation 18.93% and 20%, respectively. The overall least-squares mean for age at first semen freezing and age at first semen use was estimated as 3.14±0.09 years and 5.25±0.02 years, respectively, in Sahiwal breeding bulls. Period of freezing/use had significant effects on reproductive traits (p<0.01). Season had no significant effect on any of the traits considered in this study. CONCLUSION: It can be concluded that management inputs such as nutrition, breeding, and optimum environment should be taken care of to optimize age at first semen freezing and age at first semen use for better utilization of superior germplasm.

Optimizing age of bull at first use in relation to fertility of Murrah breeding bulls.

AIM: The aim of the present investigation was to optimize the age at first use (AAFU) of semen of Murrah breeding bulls, which will help in early selection of bulls under progeny testing program for improving the reproductive performance in the herd. MATERIALS AND METHODS: The data on AAFU, conception rate based on first A.I. (CRFAI), overall conception rate (OCR), and birth weight (B.WT) of 57 Murrah bulls during 1993-2014 at NDRI center pertaining to 14 sets of Network Project on Buffalo Improvement at ICAR-National Dairy Research Institute, Karnal, Haryana, India were adjusted for significant environmental influences and subsequently analyzed. Simple and multiple regression models were used for prediction of CRFAI and OCR of Murrah breeding bulls. Comparative evaluation of three developed models (I-III) showed that Model III, having AAFU and B.WT, fulfill the accuracy of model as revealed by high coefficient of determination, low mean sum of squares due to error, low conceptual predictive value, and low Bayesian information criterion. RESULTS: The results revealed that the average predicted CRFAI was highest (39.95%) at <3.5 years and lowest (34.87%) at >4.5 years of age at first A.I/use. Similarly, average predicted OCR was highest (41.05%) at <3.5 years and lowest (39.42%) at >4.5 years of age at first A.I/use of Murrah bulls. CONCLUSION: In organized herd under progeny testing program, Murrah bulls should be used at young age, i.e. prior to 3.5 years, which is expected to result in 5.08% better CRFAI and 1.63% better OCR in comparison to Murrah bulls used after 4.5 years of age.

Release of an active sodium transport inhibitor (ASTI) from rat hypothalamic cells in culture.

To investigate the hypothesis whether the hypothalamus releases an active (ouabain-sensitive) sodium transport inhibitor, we cultured hypothalamic and cortical cells from day 17 fetal rats. Culture media from hypothalamic cells reduced the total erythrocyte sodium efflux rate constant from 0.487 +/- (SE) 0.014 to 0.408 +/- 0.013 (P less than 0.001), and the ouabain-sensitive rate constant from 0.305 +/- 0.015 to 0.240 +/- 0.016 (P less than 0.01). Hypothalamic media also showed a dose-dependent displacement of [3H]-ouabain-binding to erythrocyte membranes. Neither cortical nor conditioned media (incubated without cells) had any effect. Various well-characterized hormones of hypothalamic origin failed to inhibit sodium efflux rate constant. These studies demonstrate that fetal rat hypothalamic cells contain and release a factor which inhibits sodium transport in human erythrocytes.

Problems and pitfalls in the isolation of an endogenous Na+, K+-ATPase inhibitor.

Plasma from volume-expanded and salt-loaded hypertensive animals and from patients with essential hypertension has been reported to inhibit Na+, K+-adenosine triphosphatase (ATPase). Inhibition of the sodium pump in vascular smooth muscle caused by such a circulating factor could increase vascular tone and sensitivity to vasoactive agents, and thereby result in arterial hypertension. Numerous efforts in the past failed to isolate the putative factor from urine and plasma. Recent studies have suggested that the hypothalamus is an important source of an endogenous Na+, K+-ATPase inhibitor, but its isolation from the tissue extracts has been rendered difficult by the presence of other cellular constituents that cause artifactual interference with the assays and purification procedures. Using an alternative approach of isolating the inhibitor from culture medium, we found that dispersed fetal rat hypothalamic neurons in a capillary culture system release a heat-stable, peptidic, low-molecular-weight, active sodium transport inhibitor that causes a reversible increase in vascular tone, sensitizes vascular smooth muscle to the vasoactive effect of norepinephrine, and possesses several characteristics of the putative endogenous digitalislike factor. This inhibitor may be a chemical mediator linking kidney, brain, and cardiovascular system in the genesis of experimental volume-expanded and salt-loaded hypertension and human essential hypertension.

Effect of low calorie intake on abnormal pulmonary physiology in patients with chronic hypercapneic respiratory failure.

To explore the effects of low calorie, low carbohydrate intake on abnormal pulmonary physiology in chronic hypercapneic respiratory failure, spirometric, arterial blood gas tension, oximetric, and electrocardiographic studies were carried out before and after weight reduction in eight patients. During a single night of monitoring, the mean basal oxygen saturation was 68.4 +/- 20.7 percent with 38 hypoxemic "dips" (a fall in oxygen saturation of more than 10 percent for one minute or longer); six patients had resting tachycardia, four had a prolonged QTc interval, three showed multiple episodes of ST-T depression, and six patients had multiple atrial and ventricular premature contractions. After a low calorie (600 kcal per day) intake for 4.4 +/- 2.3 weeks, there was a mean weight loss of 8.5 +/- 3.6 kg, the mean arterial oxygen tension increased significantly (p less than 0.005) from 55.6 +/- 9.2 to 69.1 +/- 7.9 torr, the mean arterial carbon dioxide tension fell from 59.9 +/- 9.6 to 52.4 +/- 5.4 torr (p less than 0.01), the mean oxygen saturation increased significantly (p less than 0.05) to 85.0 +/- 9.0 percent with only two hypoxemic "dips," the resting heart rate decreased from a mean of 100 +/- 19 to 90 +/- 18 beats/per minute (p less than 0.05), there was a marked reduction in ectopic activity, the ST-T depression disappeared, and the QTc interval fell in two subjects. Follow-up data in four patients suggest that the improvements achieved in arterial blood gas values can be maintained with a low calorie intake. These studies show that a low calorie, low carbohydrate intake improves all the unfavorable physiologic abnormalities in chronic hypercapneic respiratory failure.

Beneficial effects of dietary carbohydrate restriction in chronic cor pulmonale.

To explore the effects of moderate and severe reductions in carbohydrate intake on abnormal pulmonary physiology in chronic hypercapneic respiratory failure, spirometric, metabolic, arterial blood gas tension, and oximetric studies were carried out in eight patients who took, in random order daily for a week, either 50 g or 200 g of carbohydrate in an isocaloric diet. At the end of a week's daily intake of an isocaloric diet containing 200 g of carbohydrate, all patients experienced a subjective improvement; the mean body weight was 55.5 +/- 15.4 kg (1 SD) compared with 56.0 +/- 16.0 kg during the control dietary period, the arterial carbon dioxide tension decreased from a mean of 56.9 +/- 6.7 to 50.9 +/- 6.2 mm Hg (p less than 0.005), and the arterial oxygen tension increased from a mean of 50.6 +/- 7.3 to 62.0 +/- 14.5 mm Hg (p less than 0.02). After a week's intake of 50 g of carbohydrate in an isocaloric diet, the body weight and arterial oxygen tension did not change significantly, but the arterial carbon dioxide tension decreased still further to 48.0 +/- 7.8 mm Hg (p less than 0.05). Mouth pressure at 100 msec after the start of inspiration, as a measure of respiratory center output, was significantly higher during both the low carbohydrate intakes compared with the control dietary period. The spirometric data, ventilation-perfusion distribution measurements, oxygen consumption, and carbon dioxide production did not change significantly during various dietary periods. It is concluded that, under these short-term, hospital-controlled conditions, a reduction in the carbohydrate intake to 200 g a day improves the general well-being of patients with chronic hypercapneic respiratory failure, increases arterial oxygen tension, and decreases arterial carbon dioxide tension. A further reduction in the carbohydrate intake to 50 g a day provides further beneficial effects, and such a diet may be used in patients with intractable respiratory failure.

Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia.

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.