End stage renal disease among ceramic workers exposed to silica

OBJECTIVES: To evaluate whether ceramic workers exposed to silica experience an excess of end stage renal disease. METHODS: On the basis of a health surveillance programme, a cohort of 2980 male ceramic workers has been enrolled during the period 1974-91 in Civitacastellana, Lazio, Italy. For each worker, employment history, smoking data, and x ray film readings were available. The vital status was ascertained for all cohort members. All 2820 people still alive and resident in the Lazio region as in June 1994 were searched for a match in the regional end stage renal diseases registry, which records (since June, 1994) all patients undergoing dialysis treatment in public and private facilities of the region. Expected numbers of prevalent cases from the cohort were computed by applying the rate of patients on dialysis treatment by the age distribution of the cohort. RESULTS: A total of six cases was detected when 1.87 were expected (observed/expected (O/E) = 3.21; 95% confidence interval (95% CI) 1.17 to 6.98). The excess risk was present among non-smokers (O = 2; O/E = 4.34) and smokers (O = 4; O/E = 2.83), as well as among workers without silicosis (O = 4; O/E = 2.78) and workers with silicosis (O = 2; O/E = 4.54). The risk was higher among subjects with < 20 years since first employment (O = 4; O/E = 4.65) than among those employed > 20 years. CONCLUSION: These results provide further evidence that exposure to silica dust among ceramic workers is associated with nephrotoxic effects.

 

     

Selective ��4��2 Nicotinic Acetylcholine Receptor Agonists Target Epigenetic Mechanisms in Cortical GABAergic Neurons

Nicotine improves cognitive performance and attention in both experimental animals and in human subjects, including patients affected by neuropsychiatric disorders. However, the specific molecular mechanisms underlying nicotine-induced behavioral changes remain unclear. We have recently shown in mice that repeated injections of nicotine, which achieve plasma concentrations comparable to those reported in high cigarette smokers, result in an epigenetically induced increase of glutamic acid decarboxylase 67 (GAD₆₇) expression. Here we explored the impact of synthetic α₄β₂ and α₇ nAChR agonists on GABAergic epigenetic parameters. Varenicline (VAR), a high-affinity partial agonist at α₄β₂ and a lower affinity full agonist at α₇ neuronal nAChR, injected in doses of 1–5 mg/kg/s.c. twice daily for 5 days, elicited a 30–40% decrease of cortical DNA methyltransferase (DNMT)1 mRNA and an increased expression of GAD₆₇ mRNA and protein. This upregulation of GAD₆₇ was abolished by the nAChR antagonist mecamylamine. Furthermore, the level of MeCP₂ binding to GAD₆₇ promoters was significantly reduced following VAR administration. This effect was abolished when VAR was administered with mecamylamine. Similar effects on cortical DNMT1 and GAD₆₇ expression were obtained after administration of A–85380, an agonist that binds to α₄β₂ but has negligible affinity for α₃β₄ or α₇ subtypes containing nAChR. In contrast, PNU–282987, an agonist of the homomeric α₇ nAChR, failed to decrease cortical DNMT1 mRNA or to induce GAD₆₇ expression. The present study suggests that the α₄β₂ nAChR agonists may be better suited to control the epigenetic alterations of GABAergic neurons in schizophrenia than the α₇ nAChR agonists.     

Mononuclear cell reactivity to food allergens in neonates, children and adults

A model of antigen‐specific T‐cell proliferative responses based on reciprocal patterns of responses to dietary and inhalant allergens has been suggested, the former being frequent in infancy but rare in adults, whereas the latter are preserved and expand between infancy and adulthood. We have evaluated the age‐related variations of mononuclear cell reactivity to food allergens. The cord blood mononuclear cells (CBMC) of 30 neonates without family history of atopy and the peripheral blood mononuclear cells (PBMC) of 20 healthy children and of 40 healthy adults were stimulated in vitro with β‐lactoglobulin (BLG) or ovalbumin (OVA) and the cultures were harvested after 7 days. Neonates, children and adults were compared for the percentages of positive responses and for the magnitude of response. Adult subjects showed significantly lower percentages of positive responses and reduced magnitude of response than those observed in neonates and children either in BLG or in OVA cultures. We have not observed a decrease of food allergen mononuclear cell reactivity between neonates and children for the frequency of positive responses. The magnitude of response of neonates was significantly lower than that of children in BLG cultures . Our results seem to confirm the loss of mononuclear cell reactivity to food allergens in adult age. However, other reports show conflicting data. We suggest that a rigorous standardization of the methodological steps of in vitro mononuclear cell stimulation with allergen is necessary.     

Molecular analysis of β‐thalassaemia patients in a high incidence area of southern Italy

The prevalence of eight mutations in 84 patients with β‐thalassaemia major and in 16 subjects with thalassaemia intermedia was investigated. All of the patients were Italian, originating from Eastern Sicily (Messina area) and some Calabrian regions. Genomic DNA was amplified by polymerase chain reaction (PCR). DNA molecular investigations were performed by allele‐specific oligonucleotide (ASO) hybridization, to identify the following β‐thalassaemia mutations: CD39 (C‐T), IVS1‐110 (G‐A), IVS1‐6 (T‐C), IVS1‐1 (G‐A), IVS2‐745 (C‐G), IVS2‐1 (G‐A), ?87 (C‐G), CD6 A (?A). Our data underline that in thalassemia intermedia two mutations were statistically prevalent: IVS1‐6 T→C (P < 0.001) and CD 6‐A (P < 0.05). CD 39 was statistically prevalent in β‐thalassaemia major patients (P < 0.01). The difference between the two groups was not statistically significant for all the other mutations. Five different genotypes were recorded among thalassaemia intermedia and 15 among β‐thalassaemia major patients. Twenty‐five percent of the intermedia patients and 4.5% of the major patients had homozygosity for mild mutations (group I); 62.5% of the intermedia patients and 26.2% of the major patients had combinations of mild/severe mutations (group II). In addition, homozygosity or double heterozygosity for severe mutations (group III) was found in 12.5% of the intermedia patients and 69% of the major patients. Some genotypes were restricted to thalassaemia intermedia, including heterozygosity ?87/IVS1‐6 and IVS1‐6/CD 6‐A. It is essential to understand the distribution and frequency of the relevant mutations in each population where β‐thalassaemias exist. This is of particular importance for genotype–phenotype correlation and for carrier detection, genetic counselling and prenatal diagnosis.     

Stimulation of tumor growth in adult rats in vivo during an acute fast

These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.     

The functions of breathing and its dysfunctions and their relationship to breathing therapy

Breathing is unquestionably a key function of the human body; it sustains life by providing oxygen needed for metabolism and removing the by-product of these reactions, carbon dioxide. Breathing, however, has other functions apart from the ventilation of air and the maintenance of oxygen and carbon dioxide. Breathing affects motor control and postural stability and plays several roles in physiological and psychological regulation. Breathing can influence homeostatic functions in other system including the autonomic nervous system, the circulatory system, chemical regulation and metabolism.Breathing becomes dysfunctional when the person is unable to breathe efficiently or when breathing is inappropriate, unhelpful or inefficient in responding to environmental conditions and the changing needs of the individual.Impairment of the functions of breathing affects people's lives, challenging homeostasis, creating symptoms and compromising health. The efficiency with which breathing fulfills its various functions can be diminished because of musculo-skeletal dysfunction, disease, chronic psychological stress or other factors that affect respiratory drive and respiratory control. The neurological control of breathing shows high levels of neuroplasticity as shown by its ability to adapt to a wide range of internal and external conditions.Breathing therapy generally aims to either correct dysfunctions of breathing or enhance its functions. Breathing, unlike most physiological functions, can be controlled voluntarily and it can serve as an entry point for physiological and psychological regulation.     

Reorganization of GABAergic synapses in the viper optic tectum following retinal deafferentation

The immunocytochemical analysis of the viper optic tectum was carried out with an anti-gamma-aminobutyric acid (anti-GABA) antiserum following retinal deafferentation for survival times ranging from 10 to 90 days. The ultrastructure of the SGFS neuropil revealed that among the two types of axon terminals, namely pleiomorphic (P) and spherical (S) boutons, a subtype of the latter (S2), corresponding to the retinal terminals, was found to degenerate at varying rates. In most cases, this resulted in the glial engulfment of the presynaptic partner, leaving the postsynaptic differentiation free (FPSD). Beyond the two first months, the asymmetrical freed postsynaptic differentiations (FPSDs) were progressively and partly reafferented by GABA-positive P axon terminals through a sliding process. Three months postoperative, the number of GABA-positive P axon terminals which, in normal animals, establish asymmetrical contacts (1-2%), was found to increase to approximately 10%. The postsynaptic differentiation may represent a mismatched receptor area for the new competing presynaptic partners. The functional implications of such 'axonal terminal sprouting' are discussed.     

The anatomical organization of retinal projections in the shark Scyliorhinus canicula with special reference to the evolution of the selachian primary visual system

The retinal projections of the shark Scyliorhinus canicula were investigated using both the degeneration technique after eye removal and the radioautographic method following the intraocular injection of various tritiated tracers (proline, leucine, fucose, adenosine). The results showed contralateral projection via different optic tract components (TOM, AOT, TOm, TOI, ROVm, RODm) to various areas and nuclei of the hypothalamus (NSC), thalamus (NODLAT, NODMAT, NTTOM, NOVT, NODPT), pretectum (NOPC, NOCPd, NOCPv), tectum (SFGS, SGI) and mesencephalic tegmentum (AOTMd, NOTMv). Ipsilateral retinal projections were found to arborize within 7 distinct zones at the hypothalamic (NSC), thalamo-pretectal (NODLAT, NTTOM, NOVT. NOPC, NOCpd) and tectal (SFGS) levels.A comparison of the data with those previously obtained in different species of elasmobranchs and batoids indicate the existence of a common and consistent pattern of organization of the primary visual system in all selachians. Many of the discrepancies reported in studies on the organization of selachian retinal projection may be listed to methodological differences and/or interspecies variations in the cytoarchitecture of the different visual centers. Moreover, a comparison of the primary visual system of more primitive squalomorph sharks with that of the more advanced galeomorph sharks and batoids suggests that this system evolved through an increase in the neuronal density of the target structures and transformations in the dendritic configurations of the post-synaptic neurons rather than through an increase in the total number of projection zones.     

The interaction of lexical and non-lexical processing mechanisms: evidence from anomia

Patient SF presented with a selective deficit in naming, in the presence of normal auditory, visual and pictorial input processing, and of normal comprehension. The naming disorder was independent of input modality, and resulted in the inability to respond to low-frequency items. The analysis of the patient's performance in the repeated administration of the same set of pictures for oral naming and for written naming demonstrated that both tasks were disrupted to a similar extent--high consistency values were observed both across and within modality. Thus, the profile of the naming disorder observed in this patient was consistent with damage to phonological and orthographic output lexicons. SF's performance in reading and writing was apparently at odds with this account, as he was able to read aloud words with lexically-assigned stress, and to write to dictation words whose spelling is also determined lexically. The co-occurrence of the inability to activate output lexical representations in both oral and written picture naming, in the context of normal ability to activate the same representations in reading and in writing is consistent with the notion that phonological and orthographic output lexicons are distinct, but interact with nonlexical conversion mechanisms.