Embryonic Development in Invertebrates Is Arrested by Inhibitory Compounds in Diatoms.
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Journal Article↗
Biomedical subjects
G Romano
Publications and source records attributed to G Romano.
Preliminary results of a multicentre trial of the electrically stimulated gracilis neoanal sphincter.
BACKGROUND: The electrically stimulated gracilis neoanal sphincter was initially developed to treat refractory incontinence. Good early results were reported from the two centres that pioneered the technique. The aim of this study was to assess the operation in a prospective multicentre setting. METHODS: The procedure was performed on 64 patients from seven centres worldwide and was performed in stages. All patients were evaluated clinically and manometrically before and after operation. RESULTS: There was a high incidence of infective and hardware-related complications. At a median of 10 months following closure of the defunctioning stoma 56 per cent had experienced a good functional result. The major functional problems comprised evacuatory difficulties experienced by 25 per cent. CONCLUSION: The technique is effective in treating otherwise refractory incontinence. It is, however, a complex procedure and the morbidity rate may be high, particularly during the learning curve, factors that necessitate careful patient selection. Presented to the Association of Surgeons of Great Britain and Ireland in Bournemouth, UK, April 1997 and the European Council of Coloproctology in Edinburgh, UK, June 1997; and published in abstract form as Br J Surg 1997; 88(Suppl): 39 and Int J Colorectal Dis 1997; 12: 144
Adolescent↗
Hepatic resection and percutaneous ethanol injection for the treatment of selected patients with more than one hepatocellular carcinoma.
OBJECTIVE: To report our results in a selected series of patients who had two separate hepatocellular carcinomas that were not suitable for treatment by resection alone or percutaneous injection of ethanol alone, whom we treated by a combination of the two. DESIGN: Open study. SETTING: Teaching hospital, Italy. SUBJECTS: 11 patients with Child's grade A or B cirrhosis who had two hepatocellular carcinomas in distant segments of the liver. INTERVENTIONS: Percutaneous injection of ethanol into the smaller of the two nodules before, during, or after resection. MAIN OUTCOME MEASURES: Morbidity, mortality, and recurrence. RESULTS: No patient died and there was one postoperative complication (atelectasis). During a median follow-up period of 24 months (range 8-48) two patients have developed recurrences (at 10 and 18 months). CONCLUSION: Although we have studied only a few patients for a relatively short time this double approach may be an important treatment option for suitable patients with two hepatocellular carcinomas.
Adult↗
Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis.
The type 1 insulin-like growth factor receptor (IGF-1R), activated by its ligands, protects several cell types from a variety of apoptotic injuries. The main signaling pathway for IGF-1R-mediated protection from apoptosis has been previously elucidated and rests on the activation of phosphatidylinositol 3-kinase, Akt/protein kinase B, and the phosphorylation and inactivation of BAD, a member of the Bcl-2 family of proteins. In 32D cells (a murine hemopoietic cell line devoid of insulin receptor substrate 1 [IRS-1]), the IGF-1R activates alternative pathways for protection from apoptosis induced by withdrawal of interleukin-3. One of these pathways leads to the activation of mitogen-activated protein kinase, while a third pathway results in the mitochondrial translocation of Raf and depends on the integrity of a group of serines in the C terminus of the receptor that are known to interact with 14.3.3 proteins. All three pathways, however, result in BAD phosphorylation. The presence of multiple antiapoptotic pathways may explain the remarkable efficacy of the IGF-1R in protecting cells from apoptosis.
Apoptosis↗
[Thrombosis of aortic valve prostheses: its incidence, morphological aspects and surgical treatment].
BACKGROUND: The authors report their experience on the diagnosis, pathological findings and surgical treatment of prosthetic aortic valve thrombosis. METHODS: Between January 1976 and June 1998, 1289 mechanical prostheses were implanted in aortic position at our institution: a prosthetic obstruction was found in 12 cases. Thrombolysis was performed in two cases and as a result, pathological findings were not available and the patients were excluded from the study. Ten patients underwent surgical treatment. RESULTS: Thrombectomy was performed in one case and prosthetic replacement was done in 9 patients. One patient died postoperatively of low-output syndrome, the others were discharged and no recurrence of thrombosis has been observed at follow-up. Primary thrombosis was found in 6 cases, and pannus formation was observed in 4 patients. All patients with primary thrombosis had a history of poor anticoagulation. Patients with pannus formation had a tilting disc prosthesis. CONCLUSIONS: Use of bileaflet prostheses and adequate anticoagulation can further lessen the incidence of this dreadful complication.
Adult↗
[Surgical therapy of varicocele. Technical note on the inguinal approach].
BACKGROUND: There are several therapeutic proposals for idiopathic varicocele treatment, but all of them present a certain number of relapses. The technique proposed consists, through an inguinal approach, in a systematic ligation and section of all veins potentially responsible of a venous reflux. METHODS: During a period from 1990-1995 a total of 73 patients were surgically treated for idiopathic varicocele with this technique. All patients underwent preoperative spermiogram, hormonal assay and Doppler velocimetry. Through an inguinal approach, under selective spinal anaesthesia, a ligature and section of the internal spermatic vein at the internal inguinal ring is performed, followed by searching, ligature and section, of other veins responsible of venous reflux (external spermatic vein, anastomosis with sapheno-femoral veins, arteriovenous micro-anastomosis, pubic veins). The patient is discharged within twenty-four hours. RESULTS: An external dilated spermatic vein was discovered in 30.1%, pubic veins in 49.3%, anastomosis with safeno-femoral veins in 10.9% and arteriovenous micro-anastomosis in 43.8%. There were no mortality or serious postoperative morbidity; only in five cases there were complications consistent in two orchitis and three hydrocele. No relapse at follow-up (12-36 months), performed with palpation and a Doppler study, was found, while there was a spermiogram improvement in 61.6% of cases. CONCLUSIONS: This surgical approach is a safe and radical treatment without any relapse, of all types of varicocele.
Adolescent↗
The influence of furosemide on free water clearance.
BACKGROUND: Laboratory measurements of osmolality and electrolyte concentrations are useful as a source of clinical and pathophysiologic information on kidney function. We obtained different conditions of baseline diuresis in 54 rats, which were then treated with furosemide 10 mg/kg. From measurements of plasma (P) and urine (U) osmolality and Na, we calculated the free water clearance (CH2O) and the contributions of Na+ and non-Na(+)-solutes to its changes during diuretic administration. RESULTS: The results show that furosemide abolishes both urine diluting and concentrating ability, by reducing the contribution of non-Na(+)-solutes to Uosm and the formation of CH2O, while the contribution of Na+ to Posm remains unchanged. During furosemide the urines approach isosmoticity irrespective of the baseline Uosm with an asymptomatic function similar to that imposed by osmotic diuresis. It is suggested that the overflow to the concentrating sites of the nephron overwhelms their normal transport capacity independently of their baseline water permeability. The disruption of the transepithelial osmotic gradient caused by the drug impairs the transepithelial osmotic flow, leading to the excretion of isosmotic urines. CONCLUSIONS: The effect of non-Na(+)-solutes in the laboratory measurement of urine constituents can be reduced to that of plasma determination by diluting the urines according to empiric formulas derived from the present data.
Animals↗
Tubular reabsorption and sodium excretion during urine reinfusion.
BACKGROUND: The mechanisms responsible for the natriuresis that follows urine reinfusion was investigated in rats by clearance and micropuncture techniques. METHODS: In each animal two urine reinfusion periods (R1 and R2) were performed and compared to a non-urine-reinfusion, saline infusion period (S) sandwiched between them. RESULTS: Switching from urine reinfusion to an equivalent rate of saline loading was followed by a fall in Na excretion from 1.9 +/- 0.5 to 0.5 +/- 0.2% of filtered load, p < 0.002. Urine osmolality rose, and urine to plasma inulin concentration ratio rose significantly from 73 +/- 14 to 147 +/- 21 (p < 0.002). The changes in GFR, SNGFR, absolute and percent proximal reabsorption could not account for these findings. A reduced Na excretion coupled to increased urine osmolality indicates enhanced transport along a segment responsible for the urinary concentrating mechanism. Thus the data can be interpreted then as due to enhanced reabsorption along the ascending limb of Henle's loop. These changes were reversed by reinstituting urine reinfusion after the S period. The consensual changes in Na+ and K+ excretion excluded an effect of urine reinfusion on the distal exchange site. There was a continuous fall in proximal reabsorption from R1 (76 +/- 3%) to S (69 +/- 3%) to R2 (62 +/- 5%) which was inversely correlated with the changes in hematocrit (R = 0.49, p < 0.026). This indicates that part of the late diuresis and natriuresis was due to volume expansion. An osmotic effect of reinfused urine solutes was suggested by a late rise in plasma osmolality, from 312 +/- 13 to 323 +/- 8 mOsm/kg. Osmotic diuresis could have exerted additive effects upon those of volume expansion, accounting for the late fall in proximal reabsorption. CONCLUSIONS: We conclude that the acute effects of urine reinfusion are due to changes in transport of solutes and permeability to water along distal tubular segments. The changes in plasma osmolality during the last period of the present acute experiments, suggest the possibility that solute retention may be linked to the chronic effects of urine reinfusion.
Animals↗
[Chemotherapy: its repercussions on fertility and potency].
In the past twenty years, combined therapeutic regimens have improved the survival rare in many human tumors. Chemotherapy plays a significant role on this outcome. Unfortunately, many chemotherapeutic agents have adverse effects on gonadal function. The Authors examine the pathophysiology of gonadal damage in male diagnosed with cancer and treated with chemotherapeutic agents. Infertility and/or impotence can occur on these patients: the relationships between chemotherapy and tumors, towards seminal and sexual dysfunctions, are focused. Moreover, current possibilities to preserve recovery both fertility and sexual functions and discussed.
Adolescent↗
Progression from homologous to heterologous desensitization of contraction in gastric smooth muscle cells.
Acute desensitization of contraction and its relative mechanisms have been studied in smooth muscle cells isolated from guinea pig stomach. Desensitization was induced by pre-exposure of the cells to one of the excitatory neuropeptides linked to the phospholipase C intracellular cascade, i.e., cholecystokinin (CCK), gastrin-releasing peptide, and Substance P. Desensitization was homologous after a 30-s pre-exposure and heterologous if pre-exposure lasted for 5 min or longer. Homologous desensitization was studied in a more detailed way after pre-exposure to CCK. Preincubation with increasing concentrations of CCK (10 pM-1 microM) induced a progressive rightward shift of the dose-response curves associated with both a decrease in potency (ED50 4.5 pM-2.2 nM) and a maximum response that were not related to a modification of response kinetics. After brief pre-exposure to 1 nM CCK (Dmax), an inhibition of contraction was observed in response to an identical dose of CCK (45.1 +/- 8.6%), the decreased response being associated with an inhibition of inositol phosphates and [Ca++]i mobilization. Both inositol trisphosphate (InsP3)-induced contraction and [Ca++]i mobilization were inhibited to a lesser extent than CCK-induced responses. Any longer pre-exposure of cells to one of the above-mentioned neuropeptides caused heterologous desensitization, with an observed inhibition of contraction in response to all tested agonists (CCK, 60.3 +/- 5.9%; gastrin-releasing peptide: 56.7 +/- 3. 5%; Substance P, 60.6 +/- 6.5%). A similar decrease was observed in InsP3-induced contractions resulting in a desensitization of the InsP3 response as well. Full recovery of contractile responses appeared within 30 min from the end of preincubation, thus indicating that degradation of membrane receptors did not occur. Although pre-exposure of the cells to protein kinase C inhibitor GF109203X did not modify CCK-induced homologous desensitization, it blocked CCK-induced heterologous desensitization. This study demonstrates that excitatory phospholipase C-coupled enteric neuropeptides induce a time-dependent homologous as well as heterologous desensitization of smooth muscle contraction occurring at receptor and postreceptor levels.
Animals↗
Evaluation of polycyclic aromatic hydrocarbon-DNA adducts in exfoliated oral cells by an immunohistochemical assay.
Polycyclic aromatic hydrocarbon-DNA adducts were evaluated in oral cells from 98 healthy volunteers by an immunohistochemical method using a specific antiserum against benzo(a)pyrene-DNA adducts revealed by the immunoperoxidase reaction. Mean adduct content, determined as relative staining intensity by absorbance image analyzer, was significantly higher in the cells from tobacco smokers compared with nonsmokers (330 +/- 98, n = 33 versus 286 +/- 83, n = 64, respectively) with a P = 0.013 obtained by two-sample t test with equal variances. We found that in the smoker group, the PAH-DNA adduct content increases with the number of cigarettes. Thus, the relative staining intensity was 305 +/- 105 in the group smoking 1-10 cigarettes/day (n = 16), 347 +/- 77 in the 11-20 group (n = 14), and 386 +/- 112 in the group smoking more than 20 cigarettes/day (n = 3; P = 0.03 by nonparametric test for trend). No significant association was detected between PAH-DNA adducts in oral cells and variables such as residential area, oral infections, alcohol or vitamin intake, grilled food consumption, and professional activity. This work confirms and extends previous data suggesting that this immunohistochemical method might be used as a valuable dosimeter of genotoxic damage in a carcinogen-exposed population, although further studies are needed to verify the applicability of the test in high-risk populations other than smokers.
Adolescent↗
Inhibition of tumorigenesis and induction of apoptosis in human tumor cells by the stable expression of a myristylated COOH terminus of the insulin-like growth factor I receptor.
The insulin-like growth factor I receptor (IGF-IR) plays an important role in cell transformation and in protection from apoptosis. Although the wild-type IGF-IR generally has an antiapoptotic effect, there are reports that its COOH terminus may actually generate a proapoptotic signal. Three different expression plasmids, all coding for the COOH-terminal sequences of the human IGF-IR, MyCF, CF, and MyKCF, were stably transfected into human ovarian carcinoma CaOV-3 cells. All three plasmids had no effect on monolayer growth but strongly inhibited colony formation in soft agar. Only one of the plasmids, MyCF, expressing the last 112 amino acids of the IGF-IR and carrying a myristylation signal, caused large-scale apoptosis of CaOV-3 cells in vivo and abrogation of tumorigenesis in nude mice. The plasmid expressing the MyCF sequence was also introduced into human glioblastoma T98G cells, where it decreased the clonogenicity of cells, caused a marked inhibition of colony formation in soft agar, and induced apoptosis in vivo. A double mutation at residues 1293 and 1294 of MyCF completely abrogated its inhibitory and proapoptotic activities. Neither the autophosphorylation of the IGF-IR nor the tyrosyl phosphorylation of IRS-1 was affected by the expression of the MyCF plasmid. These and other findings suggest that a stably expressed myristylated COOH terminus of the IGF-IR can induce apoptosis in human tumor cells in vivo and inhibit tumorigenesis in nude mice by a mechanism that avoids the protective effect of the IGF-IR.
Animals↗
The site of action of furosemide.
To establish whether furosemide (F) acts on the proximal tubule beside the thick ascending limb of Henle's loop, we reviewed the data from 55 rats studied before and during the i.v. infusion of 10 mg kg-1 of furosemide. These animals were the object of previously published studies. SNGFR was 42.6+/-1.1 nl min-1 during baseline conditions (B), 42.7 nl min-1 during F (P>0.9). In 151 paired last proximal tubular samples, percentage reabsorption was 71.72 before and 71.72% after F (P=1.0). In 64 paired early distal tubular samples, percent reabsorption fell from 86% in B to 78% during F (P<0.0001). During F, the urine flow rate expressed as a percentage of GFR (24+/-2%) was significantly correlated (R=0.52, P<0.0001) with the percent delivery of filtrate out of the proximal tubule (26+/-3%). These data demonstrate that, even at this very high dosage, F does not act on the proximal tubule. It inhibits transport on the ascending limb of Henle's loop. By allowing the delivery of isotonic tubular fluid to the distal tubule, it causes a fall in volume absorption along the early distal convolution in proportion to its baseline water permeability. It increases urine flow by abolishing the interstitial hypertonicity and, consequently, the osmotically driven solvent flow across the distal epithelium and collecting ducts. Therefore the urine flow rate during F closely approximates volume delivery out of the proximal tubule.
Animals↗
The effect of reducing proximal tubular fluid delivery on the rate of filtration of single nephrons.
The rate of delivery of tubular fluid from the proximal tubule (PT) is thought to reset nephron filtration rate (SNGFR). In micropuncture experiments in rats we tested this hypothesis by reducing the efflux from the PT by simultaneously "double collecting" (DC) tubular fluid from the early distal tubule (DT) and from the last convolution of the PT of the same nephrons. SNGFR measured by total collection of tubular fluid was 34 +/- 3 nl/min at the DT and 34 +/- 3 nl/min at the PT (p > 0.97, n = 42). The simultaneous collection from proximal and distal sampling site was performed between these two paired measurements. It yielded an average SNGFR of 40 +/- 3 nl/min (p < 0.02). This may be due to the collection, at the distal site, of the extra amount of inulin stored between distal and proximal pipette, prior to starting the aspiration of tubular fluid. Since this error would decrease in longer collections, the difference in SNGFR between single and double collections was plotted against the duration of collections. In fact it was negatively correlated with the sampling time (p < 0.01), indicating no difference in SNGFRs for collections > 4 minutes. Reduction and complete interruption of the delivery of native proximal tubular fluid to the Macula Densa does not seem to influence the measurement of SNGFR. Filtration rate is not significantly different when measured within few minutes at the DT and PT of the same nephrons.
Animals↗
Effects of dietary cholesterol on plasma lipoproteins and their subclasses in IDDM patients.
To compare the effects of dietary cholesterol supplementation in insulin-dependent diabetic (IDDM) patients and normal subjects, 10 male IDDM patients in good glycaemic control (HbA1c 7.3+/-0.9%) (mean+/-SD) and normal plasma lipid levels, and 11 control male subjects of similar age, body mass index and lipid plasma levels underwent a double blind, cross-over, sequential study. Cholesterol supplementation of 800 mg/day or placebo were given for consecutive periods of 3 weeks. The concentration of plasma total cholesterol increased significantly with the dietary cholesterol supplementation compared to placebo in IDDM patients by 6% (p < 0.05) and in control subjects by 9% (p < 0.05). No changes were observed in the concentration of plasma triglycerides in either group. The LDL cholesterol level increased by 12% (p < 0.01) in patients and by 7% (p < 0.05) in control subjects. In patients plasma HDL cholesterol concentration remained the same, while in control subjects it tended to increase after cholesterol supplementation (from 1.14+/-0.26 to 1.23+/-0.27 mmol/l, p = 0.06). During the cholesterol intake period the mean concentration of LDL1, LDL2 and LDL3 subclasses in patients showed a significant increase by 21.0 (p < 0.05), 20.4 (p < 0.001) and 11.1% (p < 0.05), respectively, resulting in an 18.0% increase in mean total LDL mass (p < 0.001) without major changes in LDL composition. In the control subjects the changes in the concentrations of LDL subclasses during cholesterol intake were less and not significant. In the IDDM patients the cholesterol intake did not affect the concentration or composition of HDL subclasses or total HDL mass. In contrast, in control subjects cholesterol intake increased the mean concentration of HDL2a by 12.2.% (p < 0.05) and this increase was significantly different if compared to changes obtained in the patients. In conclusion, compared to normal subjects, in IDDM patients, dietary cholesterol intake increased the LDL particle mass significantly and had no positive effect on HDL.
Adult↗
Skin lesions in diabetes mellitus: prevalence and clinical correlations.
With the aim to assess the prevalence and the main clinical correlations of skin lesions in diabetes mellitus, 457 diabetic subjects consecutively attending an outpatient clinic underwent a dermatological examination. Neurovascular foot lesions were excluded. Thirty-five of 64 IDDM patients (54%) had skin alterations mainly consisting of vitiligo (9% of all patients), psoriasis (9%) and eczema (8%). The most frequent skin lesions observed in 240/393 NIDDM subjects (61%) were represented by infections (20% of all patients) and diabetic dermopathy (12.5%), while other lesions were not common. NIDDM patients with skin infections had a worse metabolic control, and those with diabetic dermopathy had a greater prevalence of neuropathy and large vessel disease than patients without skin lesions. These data show that the prevalence of skin diseases in a large, unselected diabetic population is higher than expected and indicate that, in most cases, a careful dermatological examination and a better metabolic control are needed in order to improve quality of life in these patients.
Adolescent↗
4-Aminobiphenyl-DNA adducts in laryngeal tissue and smoking habits: an immunohistochemical study.
4-Aminobiphenyl (4-ABP)-DNA adducts and p53 overexpression were evaluated in laryngeal biopsies from 38 patients by immunohistochemical methods. Samples were categorized as tumors (n = 9), polyps (n = 28) or normal tissue (n = 1). 4-ABP-DNA adducts were evaluated with a quantitative immunoperoxidase method using monoclonal antibody 3C8 in both the lesion and adjacent tissue. Relative staining intensity data showed a log-normal distribution and values found in adjacent tissue from smokers were significantly higher (median: 173.5, geometric mean: 159.9) than those measured in adjacent tissue from non-smokers (median: 75.5, geometric mean: 7.40). Statistical significance was assessed both by non-parametric testing on raw data (P = 0.0007 on rank sum test) and by parametric testing on log-transformed data (P = 0.0002 on an unpaired t-test). Furthermore, relative staining intensity in the lesional tissue showed the same significant difference between smokers and non-smokers in patients affected by polyps, whereas no significant difference was detected in patients with laryngeal tumors. Overexpression of p53, also measured with an immunoperoxidase method, was observed in 44% of the malignant tumors and in 3.5% of the polyps. This work demonstrates that 4-ABP-DNA adducts can be evaluated in laryngeal tissue and are related to smoking exposure.
Adult↗
Proximal reabsorption with changing tubular fluid inflow in rat nephrons.
The relative contribution of intraluminal versus peritubular factors in mediating glomerulo-tubular balance (GTB) is still controversial. We modulated the load of tubular fluid to the proximal tubule of single nephrons of rats by injecting oil into the efferent arteries (EAO). In fifty nephrons the changes in reabsorption induced by obstruction occurred in the same direction as, and were significantly correlated with, the simultaneous changes in single nephron glomerular filtration rate (SNGFR) (y = -0.54 + 0.92x, R = 0.91, P < 0.0001). In an additional set of thirty-nine nephrons the load of tubular fluid was changed, during EAO, by partial collection from Bowman's space or from the early proximal convolution. Thus, the rate of tubular fluid delivery along the proximal tubule was changed in an experimental situation that prevented any modification in the oncotic pressure of peritubular capillaries. The changes in proximal deliveries during this experimental condition were significantly correlated with those during reabsorption (y = -2.87 + 0.71x, R = 0.82, P < 0.0001). These data demonstrate that GTB is fully expressed even when the native peritubular environment is kept constant while the rate of perfusion of proximal tubular segments with native tubular fluid is changed.
Absorption↗