A historical approach to computing

Half a century after computers' conception, its effects, already reaching all human domains, seem to aim at becoming a universal transition similar to that one which marked in Occident the passage from artisanal production to industrial production among the 18 and 19 centuries, as from mechanisation to universal automation. It's considered that if this supposition may be correct, it would be urgent to intensify the historical approach of Informatics already present in may countries but not in ours. It's proposed the gradual incorporation of history of informatics in university careers beginning from research centers including teachers and researchers preparation, production and publication of works and the creation of museums and archives, to preserve physical testimonies and origin documents and the initial evolution of this scientific-technical invention which honours our century.     

Niflumic acid inhibits chloride conductance of rat skeletal muscle by directly inhibiting the CLC-1 channel and by increasing intracellular calcium

BACKGROUND AND PURPOSE: Given the crucial role of the skeletal muscle chloride conductance (gCl), supported by the voltage-gated chloride channel CLC-1, in controlling muscle excitability, the availability of ligands modulating CLC-1 are of potential medical as well as toxicological importance. Here, we focused our attention on niflumic acid (NFA), a molecule belonging to the fenamates group of non-steroidal anti-inflammatory drugs (NSAID). EXPERIMENTAL APPROACH: Rat muscle Cl(-) conductance (gCl) and heterologously expressed CLC-1 currents were evaluated by means of current-clamp (using two-microelectrodes) and patch-clamp techniques, respectively. Fura-2 fluorescence was used to determine intracellular calcium concentration, [Ca(2+)](i), in native muscle fibres. KEY RESULTS: NFA inhibited native gCl with an IC(50) of 42 muM and blocked CLC-1 by interacting with an intracellular binding site. Additionally, NFA increased basal [Ca(2+)](i) in myofibres by promoting a mitochondrial calcium efflux that was not dependent on cyclooxygenase or CLC-1. A structure-activity study revealed that the molecular conditions that mediate the two effects are different. Pretreatment with the Ca-dependent protein kinase C (PKC) inhibitor chelerythrine partially inhibited the NFA effect. Therefore, in addition to direct channel block, NFA also inhibits gCl indirectly by promoting PKC activation. CONCLUSIONS AND IMPLICATIONS: These cellular effects of NFA on skeletal muscle demonstrate that it is possible to modify CLC-1 and consequently gCl directly by interacting with channel proteins and indirectly by interfering with the calcium-dependent regulation of the channel. The effect of NFA on mitochondrial calcium stores suggests that NSAIDs, widely used drugs, could have potentially dangerous side-effects.     

Management of nodular sclerosis Hodgkin's disease stage I, II A and B: evidence for a beneficial effect of MOPP on the relapse rate.

85 patients with previously untreated Hodgkin's disease with stage I, II A and B nodular sclerosis were treated. 31 of them with stage I and II A were submitted to radiotherapy alone. All are alive, but 9 of them (30%) relapsed. On the contrary, 35 patients with stage I and II A, and 19 with stage I, II and IIE B were submitted to radiotherapy followed by three courses of MOPP. All 54 patients are alive and relapse-free. No severe complication related to chemotherapy was observed. The analysis of results suggests that 3 courses of MOPP can significantly (Ip < 0.00025) reduce the relapse rate in patients with stage I and II nodular sclerosis, eligible for radiotherapy, without increasing morbidity.     

Radiation-induced gadd45 expression correlates with clinical response to radiotherapy of cervical carcinoma

BACKGROUND: Recent work has identified a category of genes devoted to the control of genomic stability and prevention of cellular evolution. They encode components of cell cycle checkpoint, i.e., regulatory pathways committed to ordered cell cycle transition and fidelity of replicated DNA under adverse environmental conditions, such as those following exposure to genotoxic agents. Gadd45 belongs to the class II family of DNA damage-inducible (DDI) gene, and its role in DNA repair has been proved in many experimental models. The aim of our study was to correlate gadd45 radio-induction with the responsiveness to radiotherapy of cervical carcinomas, a type of cancer most commonly treated with radiotherapy alone. METHODS: By means of a competitive polymerase chain reaction strategy, we compared in 14 patients the gene expression levels before and during external beam radiotherapy, when a dose ranging from 18 to 25 Gy was delivered to the target. RESULTS: We found a correlation between the lack of gadd45 induction and a good clinical response to radiotherapy, in terms of both local control and disease-free survival. CONCLUSION: Our results support the measure of the induction of gadd45, and possibly of other genes required for regulated G1-S checkpoint, as a method useful for prognostic evaluation of cervical carcinoma patients.     

Methyl p-hydroxybenzoate (E-218) a preservative for drugs and food is an activator of the ryanodine receptor Ca(2+) release channel

1. Haloperidol is a drug used in the management of several psychotic disorders and its use has been linked to Neuroleptic Malignant Syndrome. In the present study we have investigated the effect of a commercial preparation of haloperidol, Serenase, on skeletal muscle sarcoplasmic reticulum. 2. Addition of Serenase to isolated terminal cisternae caused a rapid release of calcium. We tested whether the active Ca(2+)-releasing substance was haloperidol or another compound present in the preparation. 3. Our results show that methyl p-hydroxybenzoate, one of the preservatives and a commonly used anti-microbial agent (E-218) is an activator of Ca(2+) release (E.C. 50=2.0 mM), mediated by a ruthenium red-sensitive Ca(2+) release channel present in skeletal muscle terminal cisternae.     

Furosemide dynamics: influence of dietary sodium and of saralasin.

The influence of dietary sodium and saralasin on the natriuretic and diuretic response to furosemide (5 mg/kg i.v.) was studied in three groups of conscious rabbits maintained for 4 weeks on either a normal sodium diet (NSD), or a low sodium diet (LSD) or a high sodium diet (HSD). Neither the sodium content in the diet nor saralasin affected glomerular filtration rate or renal plasma flow. Compared to the NSD, an LSD did not affect the furosemide-induced increment in urinary excretion of sodium (dUNaV) but increased the increment in urinary excretion (dUV) (p less than 0.05). An HSD reduced the furosemide-induced dUNaV and dUV (p less than 0.05). Plasma renin activity (PRA) increased following furosemide administration in animals on an NSD and an LSD, but not in those on an HSD. Independent of diet, a positive correlation occurred between the increment in PRA and the dUNaV (p less than 0.001). Saralasin increased PRA and decreased baseline urinary excretion of sodium (UNaV). In addition, in rabbits on an LSD, saralasin reduced the furosemide-induced dUNaV and dUV by 34 and 27% (p less than 0.05), respectively. It is concluded that furosemide-induced diuresis is increased in rabbits on an LSD and decreased in rabbits on an HSD. In animals on an LSD, the increase in furosemide response appears to be associated with changes in the activity of the renin-angiotensin system and in rabbits on an HSD, the decrease in furosemide effect is probably the net result of several factors.     

Analysis of prognostic factors in 106 cases of carcinoma of the rhinopharynx treated with cobalt teletherapy

A series of 106 patients affected with nasopharyngeal carcinomas and treated by definitive external irradiation from January 1975 to December 1986 was retrospectively reviewed. The median follow-up, from the end of the treatment, was 43 months (range 24-90). The nasopharynx received not less than 60 Gy to the midplane: the clinically negative neck (N0) was treated with a total dose of 50 Gy and the patients who had N1-3 disease received not less than 60 Gy. Thirty-eight patients had a recurrence in the irradiated areas (31 in the nasopharynx, and 7 in the neck); 17 patients developed distant metastases. Disease-free survival at 60 months was 42%. The most significant prognostic factor (p less than 0.05) was the presence of advanced neck involvement (N2-3), since most of the lymphatic and distant recurrences were observed in this group of patients. The overall results did not reveal but slight differences in the survival according to histology, even though patients with undifferentiated carcinomas had a local recurrence rate significantly lower than those with squamous cell carcinomas. Our findings suggest that patients with N2-3 neck diseases or with locally advanced involvement (T3-4) be treated by adjuvant chemotherapy in order to decrease the risk of local and distant relapses.     

Sodium taurocholate affects prostacyclin constitutive production by cultured human vascular endothelial cells

The prostaglandin system is impaired in cholestasis; bile salts, which are a specific biochemical feature of this condition, have been shown to affect functional properties of cells and tissues, and, in some cases, their action is mediated through an alteration of prostaglandin pathway. Endothelium is a privileged site for the production and the action of arachidonate metabolites-prostacyclin in particular. To determine the effects of bile salts on the properties of vascular endothelium, cultured human endothelial cells were studied. Cholic acid sodium salt was seen to induce a direct injury on endothelial cells, as was demonstrated by a massive dismission of the intracellular radiolabel chromium 51. In the absence of detectable toxic effect, sodium taurocholate caused a significant depression of prostacyclin constitutive production from human endothelial cells. The action of sodium taurocholate was related to its concentration and to the time of exposure, and the alteration of prostacyclin production was found to be reversible. Conversely, the generation of thromboxane A2 was not influenced by this bile salt, which may suggest a specific action of sodium taurocholate on arachidonic acid metabolism. These findings indicate that bile salts may directly alter some functional properties of cultured human endothelial cells and may provide a basis for explaining some generalized manifestations that are observed in pathologic conditions characterized by cholemia.