Brucella spondylitis with paravertebral abscess due to Brucella melitensis infection: a case report

This report describes the case of a 45-year-old woman with a 5-month history of fever, generalized malaise, myalgia, lower back pain and difficulty in walking. Serodiagnosis for brucella, carried out at the onset of symptoms 5 months previously, was negative. When the patient was admitted to our hospital there was contracture of the paraspinal muscles but no peripheral nerve damage. Laboratory tests showed positive agglutination for Brucella and an increase in the rate of dilution from 1/160 to 1/640 over 2 weeks. Radiographs and a computed tomography scan of the spine revealed bone erosion in the posterior borders of the L4-L5 vertebral end plates and a soft tissue mass surrounding the interposed disc and protruding into the spinal canal. Magnetic resonance imaging confirmed the presence of a paraspinal abscess around the affected disc and tissue edema. Culture tests of the blood and abscess tissue, taken by biopsy, were negative. Rifampicin treatment (600 mg daily), combined with a bust cast to immobilize the spine, led to clinical healing without the need for surgery. Because onset symptoms are nonspecific and insidious, in nonrisk subjects a diagnosis of brucellosis may sometimes be suspected only if there are local symptoms. The phenomenon of the absence of positivity in patients with a high antibody titer should also be considered Cases such as that described herein demonstrate the need for culture tests and serodiagnosis, even in nonrisk patients with persistent fever and arthralgia, to prevent the later complications of brucellosis.     

Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration?

Metallothionein (MT)-III isoform is a brain metal-binding protein that, like the MT-I + II isoform, binds zinc with high affinity. In the young-adult age, MT-III isoform increases during transient stress while MT-I + II isoform decreases, suggesting compensatory phenomena between the two isoforms and a protective role of MT-III against oxidative damage. This role may be questioned during ageing, because the stress-like condition is chronic in ageing due to high persistent levels of interleukin-6. In the present study, high expression of MT-III and MT-I + II genes (examined by RT-PCR and in situ hybridisation) was found in the hippocampus of old rats. These results indicate that a large amount of free zinc ions can be sequestered by MT isoforms, leading to impaired zinc-dependent functions in the ageing brain. In addition, zinc (tested with the Timm's method) was found to be low in mossy fibres from the old hippocampus. As this method tests bound and unbound zinc, we also investigated free zinc ion bioavailability based on the ratio active thymulin/total thymulin. We found that zinc ion bioavailability was low in old rats, together with increased interleukin-6 mRNA, high expression of both MT isoforms and reduced number of synapses whose function is zinc-dependent, in the old hippocampus. The results indicate that concomitant increments of both MT isoforms may provoke detrimental synergistic effects leading to reduced free zinc ion bioavailability for synapses. As a consequence, compensatory phenomena between MT isoforms may not occur in the old hippocampus due to chronic stress-like condition elicited by high persistent levels of interleukin-6.     

Primary hyperparathyroidism and the presence of kidney stones are associated with different haplotypes of the calcium-sensing receptor

INTRODUCTION: Three single-nucleotide polymorphisms in the calcium-sensing receptor gene (CASR) encoding the missense substitutions A986S, R990G, and Q1011E have been associated with normal variation in extracellular calcium homeostasis, both individually and in haplotype combination. The aim of this study was to examine haplotype associations in primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Patients with sporadic PHPT (n = 237) were recruited from endocrine clinics and healthy controls (n = 433) from a blood donor clinic, and levels of serum calcium, albumin, and PTH were measured. In PHPT patients, urinary calcium/creatinine clearances and bone mineral density at spine and femoral neck were measured and the presence of kidney stones and vertebral fractures identified. The CASR single-nucleotide polymorphisms were haplotyped by allele-specific sequencing. RESULTS: Four haplotypes (ARQ, SRQ, AGQ, and ARE) of eight were observed, in keeping with significant linkage disequilibrium, but haplotype frequencies did not show significant Hardy-Weinberg disequilibrium. The SRQ haplotype was more common in PHPT (125 of 474 alleles) than in controls (170 of 866 alleles, P = 0.006) and showed a significant (P = 0.006) gene-dosage effect. There was no significant association between haplotype and bone mineral density or fractures, but association with kidney stones was significant (P = 0.0007). In the stone-forming subgroup, the SRQ haplotype was underrepresented and AGQ overrepresented. Patients bearing the AGQ haplotype had an odds ratio of 3.8 (95% confidence interval, 1.30-11.3) for presentation with renal stones compared with the rest. CONCLUSION: Our data indicate that the CASR SRQ haplotype is significantly associated with PHPT in our population. Within the PHPT patient population, the AGQ haplotype is significantly associated with kidney stones.     

NK and NKT Cells in Aging and Longevity: Role of Zinc and Metallothioneins

Introduction  During aging, dysregulated immune functions occur contributing to increased susceptibility to morbidity and mortality. However, these dysregulations are normally counterbalanced by continuous adaptation of the body to the deteriorative changes occurring over time. These adaptive changes well occur in healthy centenarians. Discussion  Both innate (natural) and adaptive (acquired) immune responses decline with advancing age. Natural killer (NK) and natural killer T (NKT) cell cytotoxicity, representing one of best models of innate immune response, decreases in aging as well as interferon-γ (IFN-γ) production by both activated types of cells. Both NK and NKT cell cytotoxicity and IFN-γ production increase in very old age with respect to normal aging, especially by NKT cells bearing TCRγδ. The role played by zinc and metallothioneins (MT) is crucial because this affects NK and NKT cell development, maturation, and functions. In particular, some MT polymorphisms are involved in maintaining innate immune response and intracellular zinc ion availability in aging with thus a role of MT genetic background to escape some age-related diseases with subsequent healthy aging and longevity.     

Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions

Aging is associated with low-grade inflammation on the one hand and mild zinc deficiency on the other. These conditions contribute to decreased immune functions, resulting in increased incidences of infections and autoimmune diseases. The aim of this study was to give more insight into the question, to what extent is low-grade inflammation caused by zinc deficient status. Here we report the effect of improved intracellular zinc status on low-grade inflammatory activity in 19 healthy elderly subjects. Our experiments show that adjustment of labile zinc by moderate zinc supplementation reduces spontaneous cytokine release and defects in termination of inflammatory activity. This results in reduced amounts of unspecific preactivated T cells and leads to improved T cell response upon mitogenic stimulation. Therefore, in contrast to other anti-inflammatory drugs, zinc does not suppress, but improves immune reaction upon pathogen invasion. These results suggest that mildly zinc-deficient, healthy elderly subjects might benefit from moderate zinc supplementation due to a more balanced immune response with reduced incidences of infections and autoimmune diseases.     

Psychosocial aspects and zinc status: is there a relationship with successful aging?

It is very interesting and innovative to study the interrelationships between biological characteristics, particularly zinc status, and psychosocial conditions in old age, because there are few and fragmentary data in the literature. The aim of this study was to examine the interrelationship between serum albumin value (an indicator of zinc status) and some psychosocial characteristics in elderly Italian volunteers recruited for the ZINCAGE project, which is supported by the European Commission in the Sixth Framework Programme (Food-CT-2003- 506850). A protocol of tests and questionnaires was used: the Lifestyle Questionnaire, the Mini-Mental Status Examination (MMSE), the Geriatric Depression Scale (GDS, 15 items), and the Perceived Stress Scale. A sample of 174 old subjects were recruited in Region Marche (Central Italy), and classified into three age groups: 65 to 74 years old, 75 to 84 years old, and >85 years old (including some nonagenarians). The preliminary results show that 69.7% of the subjects have no cognitive impairment; 66.5% have a value of the GDS scale indicating no depression; and 17% have an albumin deficiency. The majority of these are >85 years old and women. A relationship between level of albumin (used as indicator of zinc status) and depression has been found: 71% of subjects with albumin deficiency displayed a higher value on the depression test against 29% of subjects with a normal value (p < 0.01). These preliminary results show a relationship between serum albumin and psychological characteristics, in particular depression in an old Italian population. This further suggests that a zinc deficiency, via hypoalbumin values, is involved in impaired psychological characteristics in the elderly.     

Zinc homeostasis in aging: two elusive faces of the same "metal"

Proteins involved in zinc homeostasis may be altered in aging. This phenomenon may lead to zinc deficiency in the peripheral blood and an accumulation of zinc bound to insoluble aggregates at the extracellular level in the brain. Therefore, it should be more correct to talk about aging as a condition associated with zinc dyshomeostasis rather than deficiency. Restoring functional zinc homeostasis in aging people is an attractive field for antiaging research, but requires further knowledge than the current state of the art.