Pathology of experimental vitamin D deficiency rickets in growing chickens. I. Bone

Experiments were done to determine the characteristics and to study the development of avian rachitic lesions caused by vitamin D deficiency, and to investigate the cause of rickets which occurred in growing broiler chickens from 1974 to 1975 in Japan. Two kinds of vitamin D3 deficient diets, and feed of the same formula as that in use during outbreaks of rickets, were fed to day-old commercial broiler chicks until they were 7 weeks of age. Bones from the birds were examined for pathological changes at weekly intervals. Pathological changes caused by the three experimental diets were identical in character though somewhat variable in degree. The main gross lesions were marked retardation of body growth, enlargement of the ends of the long bones, hypertrophy of the bones, widening of the epiphyseal plate, thickening of the cortical bone, softening of the bone, and enlargement of the parathyroid gland. Histologically, changes at the epiphyseal plate started with widening of both proliferating and hypertrophic zones. After that, the latter became paramount, but this was soon replaced by osteoid trabeculae resulting from accelerated endochondral ossification. Finally, the epiphyseal plate consisted mostly of a conspicuously widened proliferating zone. In the metaphysis and diaphysis, abnormal endosteal and periosteal osteogenesis appeared in the fairly early stages. The porosity of the cortical bone with osteogenous tissue was due to dilatation of the canal systems and demineralisation on the walls of Haversian canals. In brief, it was observed that lesions of vitamin D deficient rickets in growing chickens varied with time and that the entire bone including the cortical bone as well as the epiphyseal plate and metaphysis was involved. From the experimental results, it appeared that the rickets which occurred in Japanese commercial flocks was due to a vitamin D deficiency. The possibility that enlargement of the parathyroid gland, hyperparathyroidism, might play an important role in the development of this disease is discussed.     

Pathology of experimental vitamin D deficiency rickets in growing chickens. II. Parathyroid gland

Histopathological studies were done on the enlarged parathyroid glands in experimental vitamin D deficiency rickets of growing broiler chickens ranging from 1 to 7 weeks of age. Two types of parenchymal cells, light and dark chief cells, were recognised in the control group. The former type of cells appeared predominantly in the stages during which bone growth was the most rapid.

The main lesions in the groups deficient in vitamin D were swelling and hyperplasia of the parenchymal cells with increased numbers of mitotic figures, a cord‐like arrangement of the cells with the formation of surrounding spaces, and a proliferation of the stromal connective tissue. Swelling and hyperplasia of the parenchymal cells, especially the light chief cells, were regarded as the most characteristic changes in hyperparathyroidism and the cord‐like arrangement of cells as the second most characteristic alteration.     

The association of vitamin D deficiency with non-alcoholic fatty liver disease

OBJECTIVE:

Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease.

METHODS:

We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease.

RESULTS:

The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl).

CONCLUSIONS:

In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.     

Cold agglutinin disease after chicken pox. An uncommon complication of a common disease.

Chicken pox, although common, is rarely associated with autoimmune hemolytic anemia. Reported here is the case of an 8-year-old boy who was found to have cold agglutinin disease and severe anemia several days after he contracted chicken pox. The cold agglutinin appeared to be a polyclonal immunoglobulin M antibody with anti-Pr specificity. To our knowledge, this is the fifth reported case of autoimmune hemolytic anemia and the second reported case of cold agglutinin disease with anti-Pr specificity to be associated with chicken pox.     

The vitamin D receptor gene is associated with Alzheimer's disease

Vitamin D may have a role in brain function. Low levels have been frequently associated with cognitive decline and may contribute to diseases of the nervous system. The vitamin D receptor (VDR) is widely expressed in human brain. Vitamin D appears to be neuroprotective and may regulate inflammation in the brain. We examined two VDR polymorphisms, Apa1 and Taq1. We used DNA from 255 Alzheimer's disease (AD) cases and 260 cognitively screened elderly controls from the longitudinal cohort of the Oxford Project to Investigate Memory and Ageing (OPTIMA). The presence of each of the linked alleles, Apa1 T and Taq1 G, was associated with the risk of AD, particularly in people <75 years old: odds ratios ≥3.0 and p ≤ 0.005. We also found preliminary evidence of interactions associated with AD between these polymorphisms and two other genes involved in the regulation of inflammation, interleukin-10 (IL10) and dopamine β-hydroxylase (DBH): synergy factors ≥3.4, uncorrected p < 0.05. These associations are biologically plausible and are consistent with a role for vitamin D in AD. Nevertheless, we consider this to be a hypothesis-generating study, which needs to be replicated in a larger dataset.     

Novel compound heterozygous mutations in the vitamin D receptor gene in a Korean girl with hereditary vitamin D resistant rickets

Hereditary vitamin D resistant rickets (HVDRR) is a rare genetic disorder caused by a mutation of vitamin D receptor (VDR) gene. A number of cases had been reported in many countries but not in Korea. We examined a three-year old Korean girl who had the typical clinical features of HVDRR including rickets, hypocalcemia, hypophosphatemia, elevated serum calcitriol level and secondary hyperparathyroidism. The girl and her father were both heterozygous for the 719C-to-T(I146T)---> c.437C > T(p.T1461) [corrected] mutation in exon 4, whereas she and her mother were both heterozygous for 754C-to-T (R154C)---> c.472 > T(p.R158C) [corrected] mutation in exon 5 of the VDR gene. In this familial study, we concluded that the girl had compound heterozygous mutations in her VDR gene which caused HVDRR. This is the first report of a unique mutation in the VDR gene in Korea.     

Studies on the pathogenesis of avian rickets II. Necrosis of perforating epiphyseal vessels during recovery from rickets in chicks caused by vitamin D3 deficiency.

This study involved comparison of the distribution and integrity of perforating epiphyseal and marrow vessels with the stage of development and integrity of chondrocytes and the distribution of insoluble calcium in the proximal tibial growth plate of 3-week-old vitamin-D3-deficient hypocalcemic chicks and 3-week-old D3-deficient chicks 12, 36, 72, and 120 hours after an oral dose of 10,000 units vitamin D3. The aim was to clarify the mechanisms responsible for chondrocyte hypertrophy and cartilage calcification in the avian growth plate. Within 12 hours after administration of vitamin D3, serum calcium levels rose to normocalcemic levels. The following morphologic changes were first recognizable at the times indicated. Distal portions of previously elongated perforating epiphyseal vessels and adjacent proliferative and maturing chondrocytes underwent necrosis by 12 hours. Chondrocyte necrosis was not preceded by hypertrophy. By 36 hours, vascular and chondrocyte necrosis involved large portions of the thickened proliferating and maturing zone, and perforating epiphyseal vessels were shortened to a normal length. By 72 hours, chondrocyte hypertrophy and calcification resumed around the shortened epiphyseal vessels. By 120 hours, marrow had removed the necrotic cartilage, and morphologically normal growth plate was restored, with perforating epiphyseal and marrow vessels, both ending in a narrow hypertropic cartilage zone. The results indicate that proximity of chondrocytes to perforating epiphyseal vessels is necessary for their viability, but loss of these vessels does not cause hypertrophy. Since hypertrophy and calcification both occur in the proximity of perforating epiphyseal vessels in normocalcemic animals but not in hypocalcemic animals, it is likely that the vessels influence hypertrophy and calcification by delivering calcium to chondrocytes.     

Toxoplasmosis presented as a submental mass: a common disease,uncommon presentation

Submental mass secondary to toxoplasmosis is not common in clinical work. A diagnosis of toxoplasmosis is rarely considered by physicians. Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. Diagnosis of toxoplasmosis was finally established by a combination of the pathological criteria, together with the positive serological finding. According to review the clinical presentations, pathological characteristics, diagnostic standard and treatment of this disease, the article aims to remind otolaryngologists who are evaluating a neck mass should be aware of the infectious cause of lymphadenopathy and the possibility of toxoplasmosis.     

Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency

Vitamin E deficiency causes a neurological disorder characterised by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage. Symptomatic vitamin E deficiency has been reported in genetic defects of the vitamin E transport protein and in malabsorption complicating cholestasis, abetalipoproteinaemia, celiac disease, cystic fibrosis and small bowel resection. There are no reports to date of vitamin E deficiency in patients with primary immunodeficiencies. We describe two CVID patients with the associated enteropathy who developed neurological disease because of vitamin E deficiency, suggesting a possible predisposition to developing this complication. We recommend that all CVID patients with evidence of an enteropathy be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological sequelae.     

Traumatic arteriovenous pial fistula masquerading as a carotid-cavernous fistula: an uncommon disorder with an unusual presentation

Traumatic intracranial pial arteriovenous fistulae are infrequent lesions. Their cardinal signs have been related to mass effect and hemorrhage, but their clinical manifestations due to venous retrograde flow into ophthalmic veins has never been described. This phenomenon is usually seen in dural arteriovenous fistula draining to the cavernous sinus or carotid-cavernous sinus fistula.A traumatic intracranial pial arteriovenous fistula arising from the supraclinoid internal carotid artery in a young patient was revealed by aggressive behavior and ophthalmologic manifestations. The endovascular management included the use of coils, stent, and ethylene-vinyl alcohol with transient balloon occlusion of the parent vessel.     

Soluble immune complex disease associated with antigen heterogeneity an HLA related disorder.

It is suggested that soluble immune complex diseases arising after infections may result from the liberation of partially synthesized bacterial polypeptide or viral nucleic acid antigens. These disrupted antigens will have heterogeneous molecular weights due to antigenic material which is incomplete as a result of premature termination of synthesis. Antigens of this type have been shown to result in significant soluble complex formation in vitro when reacted with antisera from many individuals. Interestingly, this was demonstrated using an antigen which has been instrumental in defining, in the mouse, immune response genes. These genes are known to be linked to genes which code for lymphocyte antigens. If particular immune response genes are linked to HLA types in humans, as is thought to be the case, there may be a large number of soluble immune complex diseases caused by infectious agents which may be HLA type associated.     

Asthma, allergy and respiratory infections: the vitamin D hypothesis

The recent discovery that every tissue in the human body has vitamin D receptors and that vitamin D has pleiotropic effects has prompted an increased interest in this hormone. Vitamin D deficiency is widespread and on the increase. There is no consensus on the serum vitamin D levels to consider appropriate for global health, the cutoffs for its deficiency, or the doses to use for its supplementation. Vitamin D seems to correlate closely with host reactions against various respiratory infections. Epidemiological studies have shown that low serum 25-hydroxyvitamin D levels are associated with a higher risk of upper and lower respiratory infections in children and a shortage of vitamin D may contribute to asthmatic patients' symptoms and morbidity rates. There are studies highlighting associations between childhood asthma, fetal lung and/or immune development, and maternal vitamin D intake. An insufficiency of this vitamin also seems to be implicated in the onset of childhood atopy and food allergies. The hypothesis is that vitamin D could have a central role in these pathological situations and that it may represent a novel preventive and/or therapeutic strategy. This article reviews and discusses published data on the relationship between vitamin D and asthma and allergy, emphasizing the need for controlled, prospective studies on vitamin D supplementation to clarify whether it has a role in the prevention of and treatment for asthma and allergic conditions.     

Villous adenoma of urinary tract: a common tumor in an uncommon location

The presence of colonic-type epithelium in the urinary tract is not an uncommon occurrence, but tumors derived from it are rare. Tumors arising from colonic-type epithelium, including villous adenoma and adenocarcinoma, have been reported in the renal pelvis, ureter, urinary bladder, and urethra. Villous adenomas of the urinary tract are rare, being most common in the urinary bladder, followed by the urethra. Morphologic features of these tumors are similar to those of the colonic adenomas. The largest published series of villous adenomas of the urinary tract was a study of 23 patients. This study is reviewed and other reports on villous adenomas of the urinary tract are discussed.     

Screening for vitamin D deficiency: defining vitamin D deficiency, target thresholds of treatment and estimating the benefits of treatment

Vitamin D sufficiency has been associated with improved health outcomes but cost benefit analyses of published data adopt a number of assumptions. Firstly, definitions of vitamin D deficiency vary. Secondly, available methods used for the analysis of 25-hydroxyvitamin D (25OHD) have significant limitations which could affect the adoption of specific target thresholds for treatment. Thirdly, although a variety of diseases are associated with vitamin D deficiency, randomised clinical trial data demonstrating the benefit of vitamin D supplementation only exist for the prevention of falls or fractures. This review will summarise the current evidence regarding an appropriate target threshold of 25OHD and review proposed therapeutic target thresholds of treatment. The limitations of current methods will be reviewed and objective data relating to the costs of diagnosis, the costs of treatment, and the level of evidence that screening could lessen disease burden in the community, will be provided. Finally, information needed by governments and health organisations to help justify population screening and what strategies could be adopted to make screening more cost-effective will be explored.     

Intestinal CaBP: a new quantitive index of vitamin D deficiency in the rat.

Rats raised from weaning on regiments adequate in calcium and phosphorus but deficient in vitamin D will have no detectable intestinal calcium-binding proteins (CaBP), whether or not they show other signs of vitamin D deficiency, such as hypocalcemia. When hypocalcemic, vitamin D-deficient animals were treated with 25-hydroxycholecalciferol, a vitamin D metabolite, they showed a dose-dependent increase in plasma calcium and CaBP; both responses can be described by a single linear relationship, which appears to apply whether the metabolite is 25-hydroxycholecalciferol or dihydrotachysterol. Since vitamin D status is only one determinant of plasma calcium, whereas CaBP (or its expression) appears to depend on vitamin D quantitatively, CaBP may be used as an index of vitamin D status, provided calcium intake is controlled.     

The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease.

The incidence of Alzheimer's disease (AD) increases with age and in carriers of the apolipoprotein E4 genotype. A relative deficiency of vitamin K, affecting the extrahepatic functions of the vitamin, is common in ageing men and women. The concentration of vitamin K is lower in the circulating blood of APOE4 carriers than in that of persons with other APOE genotypes. Evidence is accumulating that vitamin K has important functions in the brain, including the regulation of sulfotransferase activity and the activity of a growth factor/tyrosine kinase receptor (Gas 6/Axl). The hypothesis is now proposed that vitamin K deficiency contributes to the pathogenesis of AD and that vitamin K supplementation may have a beneficial effect in preventing or treating the disease. Vitamin K may also reduce neuronal damage associated with cardiovascular disease.