Effectiveness of melatonin treatment for sleep disturbance in orthopaedic trauma patients: A prospective, randomized control trial.

OBJECTIVES: Explore sleep disturbance in postoperative orthopedic trauma patients and determine the impact of melatonin supplementation on postoperative sleep, pain, and quality of life. MATERIALS AND METHODS: In this prospective, randomized controlled trial at a Level I trauma center, 84 adult orthopedic trauma patients with operative fracture management were randomized 2-weeks postoperatively to either the melatonin or placebo group. Patients randomized to the melatonin group (42 subjects, mean age 41.8 ± 15.5 years) received 5 mg melatonin supplements. Patients in the placebo group (42 subjects, mean age 41.3 ± 14.0 years) received identical glucose tablets. Both groups were instructed to take the tablets 30 minutes before bed for 4 weeks and received sleep hygiene education and access to the Cognitive Behavioral Therapy for Insomnia (CBT-I) Coach app. MAIN OUTCOME MEASURES: Our primary outcome was sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes were pain measured by the Visual Analog Scale (VAS), quality of life measured by the 36-Item Short Form Survey (SF-36), and opioid use. RESULTS: Patients in both groups had significant sleep disturbance (PSQI ≥ 5) at 2-weeks (83%) and 6-weeks (67%) postoperatively. PSQI improved by 3.3 points (p<0.001) at follow-up, but there was no significant difference between groups (melatonin PSQI = 5.6, placebo PSQI = 6.1, P = 0.615). Compared to placebo, melatonin did not affect VAS, SF-36, or opioid use significantly. CONCLUSION: Sleep disturbance is prevalent in orthopedic trauma patients. Melatonin treatment did not significantly improve subjective sleep quality, pain, quality of life or opioid use. LEVEL OF EVIDENCE: Therapeutic Level I.

Reverse Total Shoulder Arthroplasty Is the Most Cost-effective Treatment Strategy for Proximal Humerus Fractures in Older Adults: A Cost-utility Analysis.

BACKGROUND: Proximal humerus fractures are the second-most common fragility fracture in older adults. Although reverse total shoulder arthroplasty (RTSA) is a promising treatment strategy for proximal humerus fractures with favorable clinical and quality of life outcomes, it is associated with much higher, and possibly prohibitive, upfront costs relative to nonoperative treatment and other surgical alternatives. QUESTIONS/PURPOSES: (1) What is the cost-effectiveness of open reduction internal fixation (ORIF), hemiarthroplasty, and RTSA compared with the nonoperative treatment of complex proximal humerus fractures in adults older than 65 years from the perspective of a single-payer Canadian healthcare system? (2) Which factors, if any, affect the cost-effectiveness of ORIF, hemiarthroplasty, and RTSA compared with nonoperative treatment of proximal humerus fractures including quality of life outcomes, cost, and complication rates after each treatment? METHODS: This cost-utility analysis compared RTSA, hemiarthroplasty, and ORIF with the nonoperative management of complex proximal humerus fractures in adults older than 65 years over a lifetime time horizon from the perspective of a single-payer healthcare system. Short-term and intermediate-term complications in the 2-year postoperative period were modeled using a decision tree, with long-term outcomes estimated through a Markov model. The model was initiated with a cohort of 75-year-old patients who had a diagnosis of a comminuted (three- or four-part) proximal humerus fractures; 90% of the patients were women. The mean age and gender composition of the model's cohort was based on a systematic review conducted as part of this analysis. Patients were managed nonoperatively or surgically with either ORIF, hemiarthroplasty, or RTSA. The three initial surgical treatment options of ORIF, hemiarthroplasty, and RTSA resulted in uncomplicated healing or the development of a complication that would result in a subsequent surgical intervention. The model reflects the complications that result in repeat surgery and that are assumed to have the greatest impact on clinical outcomes and costs. Transition probabilities and health utilities were derived from published sources, with costs (2020 CAD) sourced from regional costing databases. The primary outcome was the incremental cost-utility ratio, which was calculated using expected quality-adjusted life years (QALYs) gained and costs. Sensitivity analyses were conducted to explore the impact of changing key model parameters. RESULTS: Based on both pairwise and sequential analysis, RTSA was found to be the most cost-effective strategy for managing complex proximal humerus fractures in adults older than 65 years. Compared with nonoperative management, the pairwise incremental cost-utility ratios of hemiarthroplasty and RTSA were CAD 25,759/QALY and CAD 7476/QALY, respectively. ORIF was dominated by nonoperative management, meaning that it was both more costly and less effective. Sequential analysis, wherein interventions are compared from least to most expensive in a pairwise manner, demonstrated ORIF to be dominated by hemiarthroplasty, and hemiarthroplasty to be extendedly dominated by RTSA. Further, at a willingness-to-pay threshold of CAD 50,000/QALY, RTSA had 66% probability of being the most cost-effective treatment option. The results were sensitive to changes in the parameters for the probability of revision RTSA after RTSA, the treatment cost of RTSA, and the health utilities associated with the well state for all treatment options except ORIF, although none of these changes were found to be clinically realistic based on the existing evidence. CONCLUSION: Based on this economic analysis, RTSA is the preferred treatment strategy for complex proximal humerus fractures in adults older than 65 years, despite high upfront costs. Based on the evidence to date, it is unlikely that the parameters this model was sensitive to would change to the degree necessary to alter the model's outcome. A major strength of this model is that it reflects the most recent randomized controlled trials evaluating the management of this condition. Therefore, clinicians should feel confident recommending RTSA for the management of proximal humerus fractures in adults older than 65 years, and they are encouraged to advocate for this intervention as being a cost-effective practice, especially in publicly funded healthcare systems wherein resource stewardship is a core principle. Future high-quality trials should continue to collect both clinical and quality of life outcomes using validated tools such as the EuroQOL-5D to reduce parameter uncertainty and support decision makers in understanding relevant interventions' value for money. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Non-Uremic Calciphylaxis: An Unexpected Complication With Recombinant Human Parathyroid Hormone.

Calciphylaxis is a rare syndrome of calcific microvascular occlusion, whereas non-uremic calciphylaxis (NUC) is a subset of this disease in which renal impairment is not observed. Recombinant human parathyroid hormone (rhPTH) (1-84) is a medication approved for the management of hypocalcemia in patients with hypoparathyroidism. We present a case report of a 38-year-old woman with postoperative hypoparathyroidism treated with rhPTH who subsequently developed calciphylactic lesions on her abdomen. Multidisciplinary interventions included intravenous and intralesional sodium thiosulfate therapy, laboratory monitoring, dermatological wound care, and pain management. Calciphylaxis can rarely be precipitated by rhPTH due to its effect on calcium and phosphorus balance even in the setting of normal renal function. The use of calcium and calcitriol supplementation, complicated by factors such as female sex and obesity, may have contributed in this patient's case. Hence, regular follow-up with tapering off of calcium and calcitriol supplementation is important in patients receiving rhPTH.

Physico-chemical factors controlling the speciation of phosphorus in English and Welsh rivers.

Phosphorus is a finite resource essential for global food production. However, excessive loss to river systems from diffuse sources (typically agricultural) and point sources (e.g. waste water treatment works and industrial effluent) can lead to negative environmental impacts, including changes to diatom and invertebrate community structure. Current environmental quality standards for phosphorus in the UK have been based on reactive phosphorus, which is poorly defined and comprises an unknown proportion of soluble reactive phosphorus and chemically extractable particulate phosphorus. This research assesses the influencing factors that may control soluble reactive phosphorus concentrations in rivers, including dissolved iron, as well as partitioning processes associated with the presence of total suspended solids, and questions the reliability of the assumptions used when setting environmental quality standards. The extensive phosphorus speciation monitoring carried out across a wide geographic area of England and Wales shows that not all phosphorus as measured by the molybdenum blue method is either soluble or necessarily bioavailable, particularly at concentrations in the range in which the Environmental Quality Standard for 'Good' status (typically less than 100 µg P L-1) has been set. Phosphorus speciation can change due to physico-chemical processes which vary spatially and/or temporally, including precipitation with iron and partitioning with suspended solids.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice.

Fracture healing is a complex process of many coordinated biological pathways. This system can go awry resulting in nonunion, which leads to significant patient morbidity. The Hedgehog (Hh) signaling pathway is upregulated in fracture healing. We hypothesized that the Hh signaling pathway can be pharmacologically modulated to positively affect fracture healing. Diaphyseal femur fractures were created in elderly mice (18 months, C57BL/6 females), which have a blunted and delayed healing response compared to younger mice, and were stabilized with intramedullary pins. To activate the Hh pathway we targeted the receptor Smoothened using an agonist (Hh-Ag1.5 [Hh-Ag]) and compared this to a vehicle control. Expression of Hh target genes were significantly increased in the fracture callus of the agonist group compared to controls, indicating pathway activation. Expression of osteogenic and chondrogenic-related genes was greatly upregulated in fracture callus versus intact femora, although Hh agonist treatment did not consistently enhance this response. Blindly graded, radiographic callus healing scores were significantly higher in the Hh-Ag groups at post operative day (POD) 14, indicating earlier callus bridging. On microCT, Hh-Ag treatment led to greater callus volume (+40%) and bone volume (+25%) at POD21. By day 14, callus vascularity, as assessed by 3D microCT angiography vessel volume, was 85% greater in the Hh-Ag group. Finally, mechanical strength of the calluses in the Hh-Ag groups was significantly greater than in the control groups at POD21. In conclusion, systemic administration of a Hh agonist appears to improve the osseous and vascular healing responses in a mouse fracture healing-impaired model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Novel RNA viruses within plant parasitic cyst nematodes.

The study of invertebrate-and particularly nematode-viruses is emerging with the advancement of transcriptome sequencing. Five single-stranded RNA viruses have now been confirmed within the economically important soybean cyst nematode (SCN; Heterodera glycines). From previous research, we know these viruses to be widespread in greenhouse and field populations of SCN. Several of the SCN viruses were also confirmed within clover (H. trifolii) and beet (H. schachtii) cyst nematodes. In the presented study, we sequenced the transcriptomes of several inbred SCN populations and identified two previously undiscovered viral-like genomes. Both of these proposed viruses are negative-sense RNA viruses and have been named SCN nyami-like virus (NLV) and SCN bunya-like virus (BLV). Finally, we analyzed publicly available transcriptome data of two potato cyst nematode (PCN) species, Globodera pallida and G. rostochiensis. From these data, a third potential virus was discovered and called PCN picorna-like virus (PLV). PCN PLV is a positive-sense RNA virus, and to the best of our knowledge, is the first virus described within PCN. The presence of these novel viruses was confirmed via qRT-PCR, endpoint PCR, and Sanger sequencing with the exception of PCN PLV due to quarantine restrictions on the nematode host. While much work needs to be done to understand the biological and evolutionary significance of these viruses, they offer insight into nematode ecology and the possibility of novel nematode management strategies.

The association of vitamin D supplementation with the risk of cancer in postmenopausal women.

PURPOSE: There is inconclusive evidence on whether vitamin D therapy reduces cancer risk. We investigated the effect of vitamin D (±calcium) supplementation on the risk of breast, ovarian, uterine, colorectal, and lung cancer in women. METHODS: We conducted a case-control study using the UK Clinical Practice Research Datalink (CPRD); cases were women aged ≥55 years with a first diagnosis of either breast, colorectal, lung, ovarian, or uterine cancer between 2002 and 2009, with at least 5 years of CPRD follow-up prior to the date of diagnosis, and controls were women without cancer, frequency-matched to cases by year of birth, date of study entry, length of follow-up, and general practice. The association of vitamin D supplementation with the odds of developing each cancer was determined using multivariable logistic regression, controlling for body mass index, smoking, alcohol, and deprivation. RESULTS: Ninety-seven percent of women took vitamin D with a calcium supplement. Exposure to three or more prescriptions of vitamin D was associated with a 17 % reduced odds (95 % CI 0.71-0.97) of breast cancer versus 1-2 prescriptions, but this effect disappeared when omitting women first exposed within a year of diagnosis (OR 1.0, 95 % CI 0.82-1.23). Having more than 10 prescriptions of vitamin D was associated with a 17 % lower odds (95 % CI 0.65-1.06) of colorectal cancer, but the estimates are imprecise. There was little evidence of associations of supplements with lung or gynecological cancers. CONCLUSION: We found little evidence that vitamin D (largely with calcium) supplementation is associated with decreased breast, lung, ovarian, and uterine cancer risk. There is a possible protective association between having more than 10 prescriptions of vitamin D supplements and colorectal cancer, but it requires further investigation.

Domestic source of phosphorus to sewage treatment works.

Phosphorus is an element essential for life. Concerns regarding long-term security of supply and issues related to eutrophication of surface waters once released into the aquatic environment have led governments to consider and apply measures for reducing the use and discharge of phosphorus. Examples of source control include legislation to reduce phosphorus use in domestic detergents. This research shows that other domestic sources of phosphorus also contribute significantly to the domestic load to sewer and that overall, domestic sources dominate loads to sewage treatment works. Estimates provided here show that although the natural diet contributes 40% of the domestic phosphorus load, other potentially preventable sources contribute significantly to the estimated 44,000 tonnes of phosphorus entering UK sewage treatment works each year. In the UK, food additives are estimated to contribute 29% of the domestic load; automatic dishwashing detergents contribute 9% and potentially increasing; domestic laundry 14%, including contributions from phosphonates, but decreasing; phosphorus dosing to reduce lead levels in tap water 6%; food waste disposed of down the drain 1%; and personal care products 1%. Although UK data is presented here, it is anticipated that similar impacts would be expected for other developed economies. Consideration of alternatives to all preventable sources of phosphorus from these sources would therefore offer potentially significant reductions in phosphorus loads to sewage treatment works and hence to the aquatic environment. Combining all source control measures and applying them to their maximum extent could potentially lead to the prevention of over 22,000 tonnes-P/year entering sewage treatment works.

Pollen diversity matters: revealing the neglected effect of pollen diversity on fitness in fragmented landscapes.

Few studies have documented the impacts of habitat fragmentation on plant mating patterns together with fitness. Yet, these processes require urgent attention to better understand the impact of contemporary landscape change on biodiversity and for guiding native plant genetic resource management. We examined these relationships using the predominantly insect-pollinated Eucalyptus socialis. Progeny were collected from trees located in three increasingly disturbed landscapes in southern Australia and were planted out in common garden experiments. We show that individual mating patterns were increasingly impacted by lower conspecific density caused by habitat fragmentation. We determined that reduced pollen diversity probably has effects over and above those of inbreeding on progeny fitness. This provides an alternative mechanistic explanation for the indirect density dependence often inferred between conspecific density and offspring fitness.

Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor.

Treatment of AML patients with small molecule inhibitors of FLT3 kinase has been explored as a viable therapy. However, these agents are found to be less than optimal for the treatment of AML because of lack of sufficient potency or suboptimal oral pharmacokinetics (PK) or lack of adequate tolerability at efficacious doses. We have developed a series of extremely potent and highly selective FLT3 inhibitors with good oral PK properties. The first series of compounds represented by 1 (AB530) was found to be a potent and selective FLT3 kinase inhibitor with good PK properties. The aqueous solubility and oral PK properties at higher doses in rodents were found to be less than optimal for clinical development. A novel series of compounds were designed lacking the carboxamide group of 1 with an added water solubilizing group. Compound 7 (AC220) was identified from this series to be the most potent and selective FLT3 inhibitor with good pharmaceutical properties, excellent PK profile, and superior efficacy and tolerability in tumor xenograft models. Compound 7 has demonstrated a desirable safety and PK profile in humans and is currently in phase II clinical trials.

AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).

Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.

PMMA is superior to hydroxyapatite for colony reduction in induced osteomyelitis.

Staphylococcus aureus infection is a serious complication in patients receiving orthopaedic implants. Treatment with antibiotic-loaded cements can deliver high local concentrations and reduce toxic side effects associated with systemic antibiotic administration, but polymethylmethacrylate cement is nondegradable and may necessitate additional surgery for removal. Previous studies provide support for hydroxyapatite as a biodegradable carrier, but consensus has not been achieved. We hypothesized vancomycin-loaded hydroxyapatite was superior to vancomycin-loaded polymethylmethacrylate in reducing the number of bacterial colony-forming units in the setting of osteomyelitis. Osteomyelitis was induced in rats using an established model. Animals then were randomly assigned to a control group (no antibiotics), a group treated with vancomycin-loaded polymethylmethacry-late, and two groups treated with hydroxyapatite loaded with either low-dose or high-dose vancomycin. After 6 weeks we compared the number of colony-forming units per gram of harvested bone between groups. Vancomycin-loaded hydroxyapatite was inferior to vancomycin-loaded polymethylmethacrylate in reducing the number of bacterial colony-forming units and vancomycin-loaded polymethylmethacry-late was superior to the control group. We observed no difference between low- and high-dose vancomycin-loaded hydroxyapatite groups. The poor handling properties of hydroxyapatite paste may explain these findings. Based on these results, a hydroxyapatite carrier cannot be recommended for the treatment of osteomyelitis.

Osteoporosis and skeletal fractures.

Osteoporosis affects millions of individuals worldwide, rendering them susceptible to fragility fractures of the spine, hip, and wrist and leading to significant morbidity, mortality, and economic cost. Given the substantial impact of osteoporosis on both patients and the medical community, it is imperative that physicians improve awareness and knowledge of osteoporosis in the setting of low-energy fractures. In this review, we provide information on effective means of preventing fragility fractures and introduce clinicians to issues pertinent to the patient who suffers an osteoporotic fracture. Prevention of fragility fractures centers around adequate mineral nutrition, including daily calcium and vitamin D supplementation, as well as prescription antiresorptive medications such as bisphosphonates or teriparatide therapy in severe cases, both of which have been shown to decrease future fracture risk. Balance and strength training also play important roles in the management of the osteoporotic patient, particularly following a low-energy fracture, and external hip protectors may be useful for certain patients. Kyphoplasty and vertebroplasty are two minimally invasive techniques that show great promise in the treatment of vertebral compression fractures, although questions regarding long-term biomechanical effects still exist. Traditionally, osteoporosis has been underdiagnosed and undertreated following a low-energy fracture in an elderly patient. Although treatment rates may be improving through public health initiatives, the majority of patients with osteoporosis remain inadequately treated. Perioperative intervention programs that focus on patient education about osteoporosis and treatment options lead to significant increases in intervention and treatment. Reducing the risk of skeletal fractures in patients susceptible to osteoporosis involves improved physician education on the risk factors and management of osteoporosis, as well as informing patients on the significance of dual-energy X-ray absorptiometry testing and medical treatment so that they may serve as their own healthcare advocates in this often-undertreated disease.

Improvement in the undertreatment of osteoporosis following hip fracture.

BACKGROUND: Osteoporosis is a common disease characterized by decreased bone mass and increased fracture risk in postmenopausal women and the elderly. Hip fractures are among the most common consequences of osteoporosis and unfortunately usually occur late in the course of the disease. When a patient is admitted to the hospital with a fragility hip fracture, a unique opportunity for diagnosis and treatment presents itself. Fortunately, several medications have proven to be effective in lowering the risk of future fractures. The purposes of the present study were to test the hypothesis that most fragility hip fractures go untreated and to determine whether educational efforts to raise physician awareness have led to an improvement in osteoporosis treatment rates. METHODS: A retrospective cohort study was performed with use of the patient databases at two university medical centers and one university-affiliated community hospital. The charts of 300 randomly selected patients were sorted with use of ICD-9 (International Classification of Diseases, Ninth Revision) codes for femoral neck fractures. There were 100 patients from each center, with twenty-five patients from each year between 1997 and 2000. The admitting diagnosis, mechanism of injury, admission medications, procedures performed during hospitalization, and discharge medications were then extracted and analyzed. During this period, the National Osteoporosis Foundation established guiding principles for the treatment of fragility fractures. RESULTS: Of the seventy-five patients from all centers for each year from 1997 to 2000, 11%, 13%, 24%, and 29%, respectively, were discharged with a prescription for some medication targeting osteopenia, either supplemental calcium or an antiosteoporotic medication (estrogen, calcitonin, a bisphosphonate, or raloxifene). A trended chi-square analysis of this increase revealed a p value of <0.001, indicating that this improvement in treatment was unlikely due to chance alone. Fifty-eight (19.3%) of the 300 patients in the study received a prescription at the time of discharge. However, forty of these patients (13.3% of the overall group) received calcium and only eighteen (6.0% of the overall group) received a medication to actively prevent bone resorption and treat osteoporosis. In addition, no patient underwent a bone density scan while in the hospital. CONCLUSIONS: Elderly patients and postmenopausal women who are admitted to the hospital and diagnosed with a low-energy femoral neck fracture have been undertreated for osteoporosis. However, over the four years of the present study, there was a significant increase in the rate of treatment. It is hoped that treatment rates will continue to increase in the future with continued educational efforts.

The embryocidal effect of Zinc (Zn) and Cadmium (Cd) in pregnant Mona strain rats

OBJECTIVE: To investigate the toxicity of zinc and cadmium on pregnant Mona strain rats. METHODS: A total of 21 female rats, divided into 3 groups of 7 rats each, were mated, and on the 8th day of gestation, these pregnant rates were injected subcutaneoulsly with 3 mg/kg Zinc sulphate, Group 1:3 mg/kg Cadmium sulphate, Group II, and normal saline, Group III. Animals were fed purina lab chow and given water ad libitum. On the 15th day, animals were sacrified with ether, the uteri were removed and examined. Observations on embryocidal effects and foetal abnormalities were recorded. RESULTS: Zinc at a dose of 3 mg/kg administered subcutaneously on the 8th day of gestation had a marked embryocidal effect (13.8 percent). This was observed to a much lesser degree (1.5 percent) with Cd treatment. CONCLUSION: The results demonstrate the need for further research and a degree of caution in recommending the liberal use of zinc as a dietray supplement (especially in pregnancy). Further detailed analysis of the degree of air pollution and the vegetable material grown in areas with high concentrations of heavy metals is recommended.(Au)

Effects of aqueous extract of neem (azadirachta indica a. juss) on streptozotocin induced diabetic rats

Neem (Azadirachta indica) products have been extensively used in Ayurvedic medicine in India for many centuries. To elucidate a common folkloric saying, "two leaves a day keeps diabetes away", thirty male Wistar rats weighing between 180 to 250 g were randomly assigned to three equal groups. To induce diabetes, rats in groups II and III received a single intraperitoneal dose of Streptozotocin (STZ) at a rate of 50 mg/Kg body weight. After 5 days of STZ treatment, diabetic rats in group III received 0.4 percent aqueous neem extract in drinking water for 188 days. Rats in group III received citrate buffer and served as drinking water for 188 days. Rats in group I received citrate buffer and served as control. All the rats were maintained under standard management conditions and received water/extract and dry pellet diet ad libitum. The animals were sacrificed after 290 days for histological examination of various tissues. The results of the study revealed that (1) the mean blood glucose levels showed a decreasing trend (p>0.05) during 48-77 days of neem treatment and also after 51 days of discontinuation of the neem treatment (2) the percent gain in body weight in neem treated diabetic rats was lower than in diabetic rats (20v/s 80 percent) (p value). In conclusion, the aqueous extract of neem showed significant improvements in the body weights and lessened mortality in STZ induced diabetic rats but could not normalise blood glucose levels.(AU)

Effect of aqueous Neem (azadirachta indica) extract on testosterone and other blood constituents in male rats: a pilot study

Effect of oral administration of crude aqueous neem extract on serum testosterone and other blood constituents was studied in the male Wistar rats for 10 weeks. The neem treatment resulted in significant decreases (p,0.01) in total testosterone, total bilirubin and K+ in serum. There were also increases (p<0.05) in packed cell volume, mean corpuscular haemoglobin concentration, red blood cell, white blood cell and lymphocyte counts without showing any cytotoxic effects in the body.

Toxic effects of ackee oil (Blighia sapida L) following subacute administration to rats

Subacute intraperitoneal administration of the lipid portion of the unripe ackee arillus, referred to as "ackee oil", resulted in marked neutropenia (p<0.001) and increase in platelets (p<0.01) without anaemia, in rats. Blood urea, sodium amd aspartate aminotransferase levels were significantly decreased but glucose and bilirubin levels were similar to those of controls. The lungs showed areas of petechial haemorrhaghes and a dose-related perivascular and peribronchial mononuclear cell infiltration. The pulmonary toxicity may be interpreted as a hypersensitive reaction to ackee oil. Further research is in progress on the neutropenic effects of ackee oil. (AU)