Metabolic Characterization of Dairy Cows Treated with Gossypol by Blood Biochemistry and Body Fluid Untargeted Metabolome Analyses.

To characterize the metabolic disorders of dairy cows treated with gossypol, 12 dairy cows were assigned to either a control group or a treatment group that was fed 1000 mg of gossypol per kilogram of dry matter feed for 28 days. Milk quality was adversely affected, as both milk protein and lactose levels were significantly decreased in the gossypol-treated group (3.40% vs 3.16%, P = 0.044; 5.15% vs 4.91%, P = 0.027; respectively). Plasma samples revealed increases in alanine aminotransferase (P = 0.092), choline esterase (P = 0.02), and glutathione transferase (P = 0.0005) and decreases in glucose (P = 0.076) in the gossypol-treated group. Mass spectrometry based comparative metabolomic analyses showed reduced concentrations of the gluconeogenesis precursor l-glutamine (P = 0.047), with significant decreases (P < 0.05) in plasma l-lysine, l-threonine, and homoserine levels after gossypol treatment. HDL-C and LDL-C levels in the gossypol-treated group were increased (P = 0.044) and decreased (P = 0.023), respectively. These results demonstrate that gossypol induced oxidative stress and hepatotoxicity; reduced peripheral lipid metabolism, and enhanced hepatic lipid accumulation; decreased amino acid bioavailability and milk protein synthesis; and decreased gluconeogenesis and milk lactose in dairy cows.

Determination of trace nickel in hydrogenated cottonseed oil by electrothermal atomic absorption spectrometry after microwave-assisted digestion.

Microwave digestion of hydrogenated cottonseed oil prior to trace nickel determination by electrothermal atomic absorption spectrometry (ETAAS) is proposed here for the first time. Currently, the methods outlined in U.S. Pharmacopeia 28 (USP28) or British Pharmacopeia (BP2003) are recommended as the official methods for analyzing nickel in hydrogenated cottonseed oil. With these methods the samples may be pre-treated by a silica or a platinum crucible. However, the samples were easily tarnished during sample pretreatment when using a silica crucible. In contrast, when using a platinum crucible, hydrogenated cottonseed oil acting as a reducing material may react with the platinum and destroy the crucible. The proposed microwave-assisted digestion avoided tarnishing of sample in the process of sample pretreatment and also reduced the cycle of analysis. The programs of microwave digestion and the parameters of ETAAS were optimized. The accuracy of the proposed method was investigated by analyzing real samples. The results were compared with the ones by pressurized-PTFE-bomb acid digestion and ones obtained by the U.S. Pharmacopeia 28 (USP28) method. The new method involves a relatively rapid matrix destruction technique compared with other present methods for the quantification of metals in oil.

Accidental human injection of Excenel RTU: ceftiofur hydrochloride in cottonseed oil.

INTRODUCTION: There is little knowledge within the medical community of the existence of veterinary antibiotics in oil-based suspensions and the adverse effects that may occur with accidental human injection. CASE REPORT: A farmer injected an unknown quantity of Excenel RTU into her right thigh. Despite early debridement she developed a deep infection and recurrent chronic inflammation in the subcutaneous tissues and muscle secondary to the cottonseed oil suspension. Radical debridement and extensive split skin grafting was required but she still has had recurrences 12 months after injury. DISCUSSION: Prompt surgical debridement should be performed as in cases of oil based veterinary vaccines. Despite being an antibiotic there is a significant risk of infection from a dirty needle following inoculation and multiple cultures should be taken and appropriate broad spectrum antibiotics used. Radical debridement and skin grafting necessitating specialist plastic surgical attention may be required.

Prevalences of oligozoospermia and azoospermia in male partners of infertile couples from different parts of India.

AIM: To determine whether there was any regional variation in the prevalence of azoospermia, oligozoospermia and mean sperm counts in male partners of infertile couples from different parts of India. METHODS: Data on 16,714 semen samples analyzed over the past five years from six different laboratories located in five cities of India were collated and evaluated. RESULTS: There was a regional variation in the prevalence of azoospermia. The prevalence of azoospermia was extremely high in Kurnool and Jodhpur (38.3% and 37.4%, respectively). There was also a regional variation in the prevalence of oligozoospermia (51%) in Kurnool. There was no significant difference in the mean sperm counts in normospermic men. CONCLUSION: There is a regional variation in the prevalence of azoospermia and oligozoospermia in the male partners of infertile couples from different regions of India. The prevalence of azoospermia in Kurnool and Jodhpur is higher than any other worldwide reported literature. Further studies need to be carried out to determine the cause of this.

Gossypol isomers bind specifically to blood plasma proteins and spermatozoa of rainbow trout fed diets containing cottonseed meal.

We investigated the role of gossypol isomers binding to blood plasma, seminal plasma and spermatozoa to elucidate gossypol anti-fertility action in the teleost fish, rainbow trout (Oncorhynchus mykiss). Growth and hematological indicators of males were depressed when fish meal protein in diets was completely replaced with cottonseed meal. The cottonseed meal contained equal proportions of (-) (47.8+/-1.6%) and (+) gossypol isomers. Concentrations of spermatozoa were decreased with increasing proportions of gossypol in diets (from 0.22% to 0.95%); however, sperm motility and fertilizing ability were not affected. In contrast to mammals, steroid hormone concentrations were not suppressed in fish given diets with gradual increase of gossypol level. Gossypol concentrations were 100-fold higher in blood plasma than in seminal plasma, confirming a barrier in gossypol transfer between the general circulation and the testis. Spermatozoa accumulated predominantly (+) enantiomer (65-75%) with decreasing proportions as dietary gossypol concentrations increased. Spermatozoa bound most of the gossypol contained in the semen; however, this did not result in impairment of the sperm motility apparatus. Teleost fish sperm rely on ATP stores that accumulate during maturation as a source of energy during activation. In addition, the duration of sperm movement is short in these fish. As such, we hypothesize that the major action of gossypol on mammalian sperm, which is uncoupling of oxidative phosphorylation, does not impair the energy supply required for flagellar beating in fish spermatozoa.

Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate.

In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17beta-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with alpha-hydroxy and beta-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane.

Acidos grasos esenciales en la producción actual de oleaginosas de la República Argentina: posibilidades futuras de diversificación / Essential fatty acids in the present vegetable oils production of the República Argentina: future possibiities in the diversification trends production

Se presenta un resumen de los logros alcanzados durante casi 50 años en un tema fundamental del conocimiento de las características de composición acídica de aceites vegetales de producción masiva en la república Argentina. Su desarrollo, en parte coincidente con la evolución del conocimiento analítico, ha sido de utilidad a la nutrición, normalización, legislación alimentaria, tecnología, uso y contralor de aceites vegetales y de pulpa de frutos. El progreso observado en los avances de modernas técnicas de la Biotecnología tiende a una apertura en la diversificación de la producción

Acidos grasos esenciales en la producción actual de oleaginosas de la República Argentina: posibilidades futuras de diversificación / Essential fatty acids in the present vegetable oils production of the República Argentina: future possibiities in the diversification trends production

Se presenta un resumen de los logros alcanzados durante casi 50 años en un tema fundamental del conocimiento de las características de composición acídica de aceites vegetales de producción masiva en la república Argentina. Su desarrollo, en parte coincidente con la evolución del conocimiento analítico, ha sido de utilidad a la nutrición, normalización, legislación alimentaria, tecnología, uso y contralor de aceites vegetales y de pulpa de frutos. El progreso observado en los avances de modernas técnicas de la Biotecnología tiende a una apertura en la diversificación de la producción

Effects of gossypol and cottonseed products on reproduction of mammals.

Gossypol is a toxic factor indigenous to the cotton plant genus Gossypium. Concentrations of free gossypol contained in feedstuffs such as whole cottonseed and cottonseed meals vary considerably. Nonruminant animals are particularly sensitive to the toxic effects of gossypol, whereas ruminants are somewhat more resistant. Signs of gossypol toxicosis in nonruminants, preruminants, and ruminants are similar and include labored breathing, dyspnea, decreased growth rate, and anorexia but are not pathognomonic. Postmortem findings include generalized edema and congestion of lungs and liver, fluid-filled thoracic and peritoneal cavities, and degeneration of heart fibers. The antifertility effect observed in many nonruminant species is overshadowed by toxic effects, particularly in females. Gossypol seems to disrupt estrous cycles, pregnancy, and early embryo development in females of all nonruminant species studied. Probable mechanisms include an endocrine effect on the ovary as well as a cytotoxic effect on the uterus or embryo. The female ruminant seems to be relatively insensitive to the antifertility effect of gossypol; however, in vitro data indicate some inhibition of embryonic development and ovarian steroidogenesis. The antifertility effect of gossypol has been studied most in males of nonruminant species. The effects of gossypol in the male are both dose- and time-dependent. At effective doses, gossypol causes males to be infertile because of sperm immotility and depressed sperm counts. Specific mitochondrial damage in the tails of spermatozoa seems to render them immotile, and extensive damage to germinal epithelium may be responsible for depressions in spermatogenesis. In ruminant males fed diets containing gossypol, ejaculated sperm appears normal under light microscopy. The integrity of the membrane of sperm cells may be damaged. Extensive damage to the germinal epithelium has been shown in both rams and bulls fed diets containing gossypol and is of major concern.

Effects of dietary cottonseed meal and iron-treated cottonseed meal in different laying hen genotypes.

The effects of dietary screw-pressed cottonseed meal (CSM) and iron-treated CSM on laying performance and discolourations in eggs were examined in a range of hen genotypes. In experiment 1, six genotypes, obtained at point-of-lay from various sources, were fed on a non-CSM diet, a diet with 300 g CSM/kg, and a diet containing iron-treated CSM at 300 g/kg. In experiment 2, two of these genotypes were reared together from day-old and were fed from 10 to 18 weeks on a non-CSM diet or a diet containing iron-treated CSM at 250 g/kg. They were then fed on a non-CSM layer diet or a diet containing iron-treated CSM at 300 g/kg, in a 2 x 2 x 2 factorial design that also examined the effects of the rearing diet. 2. The effects on food intakes and egg production of including CSM and iron-treated CSM in layer diets depended on the genotype of the hens. The strongest interaction between breed and diet was on food intake, the breed Hubbard Golden Comet (HGC) being the least tolerant of CSM and iron-treated CSM. 3. Inclusion of iron-treated CSM in the rearer diet to supply approximately 70% of the dietary protein had no adverse effects on growth or age at first egg. Food intake and egg production between 18 and 26 weeks were affected by the iron-treated CSM layer diet, but there were no carry-over effects attributable to the rearing diets. 4. Genotype was not a factor in the development of the gossypol-related brown yolk discolouration in fresh or warm-stored eggs of hens fed on a CSM-based diet containing 197 mg free gossypol/kg and 52 mg cyclopropenoid fatty acids (CPFA)/kg (experiment 1). 5. In both experiments, the susceptibility of eggs to the CPFA-related cold storage effects depended on the genotype of the hen, eggs from hens of the HCG breed being more affected than those of ISA hens. 6. Treatment of CSM with crystalline ferrous sulphate heptahydrate, at a 4:1 weight ratio of iron to free gossypol, prevented brown yolk discolourations in all genotypes tested, as assessed by subjecting egg yolks to atmospheres of ammonia, and cold storage of eggs.

Premature farrowings caused by feeding cottonseed meal.

Increasing the level of cottonseed meal (CSM) in sow diets from less than 5% to 10% increased the incidence of premature farrowings (gestation length less than 111 days) from 1.1% to 2.7% (p less than 0.001) and reduced the mean gestation length from 114.07 +/- 1.53 to 113.70 +/- 1.59 days (p less than 0.0001). Survival of piglets born prematurely was poor. After removal of CSM from the diet there was a residual effect lasting several weeks before the gestation length returned to normal. Experimental feeding of diets containing 20% and 40% CSM to small groups of sows caused significant shortening of gestation length and 3 of 26 sows fed 40% CSM farrowed prematurely. The mechanism by which CSM causes this effect has yet to be determined.

The effect of long-term treatment with crude cotton seed oil on pituitary and testicular function in men.

In a previous study, compensatory dysfunction of the Leydig cell was identified in men in whom spermatogenesis had failed to recover after gossypol treatment. In this study, LHRH- (100 micrograms i.v.) and hCG (3000 IU i.m.)-stimulation tests were conducted in four controls and in 45 men who had used crude cotton seed oil as their cooking oil. The patients were divided into two groups: group A--17 men with normospermia or oligospermia and group B--28 men who were azoospermic. The basal serum LH and FSH concentrations were within the normal range in group A, whereas those in group B were increased markedly. There was no significant difference in testosterone levels between the two groups, although the levels were significantly lower than in the controls. The response of LH and FSH to LHRH, and of testosterone to hCG stimulation, were within the normal range in group A, whereas in group B the response to the LHRH test was increased significantly while their response to the hCG test was reduced markedly. It was concluded that the functions of the pituitary and Leydig cells remained unchanged in group A after long-term use of crude cotton seed oil, and that once azoospermia has occurred, it is followed by total testicular failure as indicated by the responses to LHRH and hCG tests.

Cottonseed hypersensitivity: new concerns over an old problem.

Seven subjects, who experienced systemic allergic reactions after the ingestion of a newly marketed food supplement, were evaluated to identify the responsible ingredient. Skin testing with extracts prepared from ingredients in the food supplements revealed marked sensitization of all of the subjects to cottonseed protein. Double-blind, placebo-controlled food challenges performed in two subjects with cottonseed flour produced reactions consisting of oropharyngeal pruritus, rhinitis, nausea, diaphoresis, dyspnea, cough, and a fall in pulmonary function tests of 45% or more. All placebo challenges were negative. Because of the reactions observed during these challenges, other subjects were not challenged orally with cottonseed protein but consumed without incident other ingredients in the supplement to which they were skin test positive. Our evaluation strongly incriminates cottonseed protein as the cause of the systemic allergic reactions in these subjects and is consistent with earlier articles in the literature describing the potent allergenicity of cottonseed protein.

Angioedema and urticaria caused by cottonseed protein in whole-grain bread.

A 29-year-old patient developed a severe allergic reaction after eating whole-grain bread. The bread appeared to contain cotton seed-protein flour. The skin prick tests with the bread and cottonseed were strongly positive. High level of circulating antibodies of IgE class against cottonseed protein could be detected in her blood samples. It is evident that cottonseed flour is used in diverse products and can cause unexpected severe hypersensitivity reactions.