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Biomedical subjects

E Reda

Publications and source records attributed to E Reda.

At least 19 recordsLinked to original sources
PubMed2003

The carnitine system and body composition.

Carnitine is a trimethylamine molecule that plays a unique role in cell energy metabolism. Mitochondrial betaoxidation of long-chain fatty acids, the major process by which fatty acids are oxidized, is ubiquitously dependent on carnitine. Control of mitochondrial beta-oxidation through carnitine adapts to differing requirements in different tissues. The physiological role of carnitine and its system in body composition is understood from insights into skeletal muscle metabolism, which converge into the metabolic heterogeneity of muscle fibers, and contractile properties that are correlated with phenotypes of resistance to fatigue. In skeletal muscle, the importance of the function of the carnitine system in the control and regulation of fuel partitioning not only relates to the metabolism of fatty acids and the capacity for fatty acid utilization, but also to systemic fat balance and insulin resistance. The carnitine system is shown to be determinant in insulin regulation of fat and glucose metabolic rate in skeletal muscle, this being critical in determining body composition and relevant raised levels of risk factors for cardiovascular disease, obesity, hypertension, and type 2 diabetes.

Animals↗
PubMed2000

Carnitine: an osmolyte that plays a metabolic role.

Carnitine, gamma-trimethyl-beta-hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic ones. It is the sole source of carbon and nitrogen in some bacteria; it serves as osmoprotectant in others. It is a carrier of acyl moieties, and exclusively of long-chain fatty acids for mitochondrial beta-oxidation in mammals. The conspicuously similar composition of the intracellular milieu among widely different species in relation to organic osmolyte systems involves the methylamine family to which carnitine belongs. This prompted us to examine the osmolytic properties of carnitine in an attempt to clarify the metabolic functions carnitine has acquired during evolution. An understanding of the metabolic functions of this organic compatible solute impinge on research involving this compound.

Animals↗
PubMed2000

Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system.

An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.

Antineoplastic Agents↗
PubMed2000

Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and pathological conditions.

This review focuses on the regulation of myocardial fatty acids and glucose metabolism in physiological and pathological conditions, and the role of L-carnitine and of its derivative, propionyl-L-carnitine. Fatty acids are the major oxidation fuel for the heart, while glucose and lactate provide the remaining need. Fatty acids in cytoplasm are transformed to long-chain acyl-CoA and transferred into the mitochondrial matrix by the action of three carnitine dependent enzymes to produce acetyl-CoA through the beta-oxidation pathway. Another source of mitochondrial acetyl-CoA is from the oxidation of carbohydrates. The pyruvate dehydrogenase (PDH) complex, the key irreversible rate limiting step in carbohydrate oxidation, is modulated by the intra-mitochondrial ratio acetyl-CoA/CoA. An increased ratio results in the inhibition of PDH activity. A decreased ratio can relieve the inhibition of PDH as shown by the transfer of acetyl groups from acetyl-CoA to carnitine, forming acetylcarnitine, a reaction catalyzed by carnitine acetyl-transferase. This activity of L-carnitine in the modulation of the intramitochondrial acetyl-CoA/CoA ratio affects glucose oxidation. Myocardial substrate metabolism during ischemia is dependent upon the severity of ischemia. A very severe reduction of blood flow causes a decrease of substrate flux through PDH. When perfusion is only partially reduced there is an increase in the rate of glycolysis and a switch from lactate uptake to lactate production. Tissue levels of acyl-CoA and long-chain acylcarnitine increase with important functional consequences on cell membranes. During reperfusion fatty acid oxidation quickly recovers as the prevailing source of energy, while pyruvate oxidation is inhibited. A considerable body of experimental evidence suggests that L-carnitine exert a protective effect in in vitro and in vivo models of heart ischemia and hypertrophy. Clinical trials confirm these beneficial effects although controversial results are observed. The actions of L-carnitine and propionyl-L-carnitine cannot be explained as exclusively dependent on the stimulation of fatty acid oxidation but rather on a marked increase in glucose oxidation, via a relief of PDH inhibition caused by the elevated acetyl-CoA/CoA ratio. Enhanced pyruvate flux through PDH is beneficial for the cardiac cells since less pyruvate is converted to lactate, a metabolic step resulting in the acidification of the intracellular compartment. In addition, L-carnitine decreases tissue levels of acyl moieties, a mechanism particularly important in the ischemic phase.

Animals↗
PubMed1996

Is contralateral exploration of the kidney necessary in patients with Wilms tumor?

PURPOSE: Surgical exploration of the contralateral kidney in patients with Wilms tumor is standard practice. The introduction of modern imaging techniques (ultrasound, computerized tomography and magnetic resonance imaging) in place of excretory urography has led to a more accurate definition of intrarenal pathology. Is contralateral kidney exploration still necessary in patients with Wilms tumor? MATERIALS AND METHODS: We reviewed the records of 75 patients from 3 medical centers who were evaluated and treated for Wilms tumor in the last 14 years. All children underwent preoperative excretory urography, computerized tomography, ultrasound and/or magnetic resonance imaging. RESULTS: Seven bilateral Wilms tumors were diagnosed preoperatively and confirmed surgically, whereas extensive operative exploration of the contralateral kidney in the other 69 patients revealed no additional pathological condition. This concurred with preoperative radiological findings with 100% sensitivity and specificity. Furthermore, 1 month to 12 years of followup (mean 4.3 years) revealed no tumor in the contralateral kidney. The major postoperative complication was small bowel obstruction in 5 patients 15 to 180 days (mean 77.2) after explorative laparotomy. CONCLUSIONS: In all patients preoperative radiological investigation was accurate in excluding bilaterality. With modern imaging techniques and effective chemotherapy extensive contralateral renal exploration may no longer be mandatory for managing Wilms tumor.

Adolescent↗
PubMed1994

Acetyl-L-carnitine prevents age-dependent structural alterations in rat peripheral nerves and promotes regeneration following sciatic nerve injury in young and senescent rats.

Morphologic and morphometric alterations of the sciatic nerve from old Sprague-Dawley rats and of lesioned tibial nerve from young and senescent Sprague-Dawley rats were studied. The possible therapeutical effects of treatment with acetyl-L-carnitine (ALCAR) were also investigated, ALCAR being a compound shown to exert a beneficial pharmacological action on diabetic neuropathies. Nerve sections from animals sacrificed under anesthesia were stained with toluidine blue. In old rats, a 6-month treatment with ALCAR markedly reduced the percentage of myelinated fibers (MF) characterized by age-dependent morphologic alterations (4% in treated rats versus 11% in untreated ones), such as myelin balloons, infolded loops of myelin, myelin reduplication, and ovoids. In the lesioned animals, ALCAR-treatment (15-60 days for young rats and 6-9 months for senescent rats) produced a significant increase versus controls in the density of regenerating myelinated fibers (RMF) at 15 days (young rats) and at 30 days (senescent rats) after crush, as well as an increase in the axon diameter in both young and senescent rats at 60 days after nerve crush. The MF diameter (sheath + axons) was significantly larger in treated senescent rats than in controls at 100 days after nerve crush. In ALCAR-treated rats, both young and senescent, the density of degenerative elements was lower and the RMF ratio (RMF density/RMF density + density of degenerative elements) was higher than that in controls at all detection times.

Acetylcarnitine↗
PubMed1994

Optimal renal preservation with timely percutaneous intervention: a changing concept in the management of blunt renal trauma in children in the 1990s.

OBJECTIVE: To report the results of treatment of 132 children with blunt renal trauma and indicate our treatment recommendations. RESULTS: Between 1971 and 1991 132 children presented with blunt renal trauma. Grade I injuries (renal contusion) were seen in 97 children, grade II injuries (renal laceration) in 32 and grade III (shattered kidney and pedicle injury) in three. Twenty-six children with grade II injuries were treated non-surgically. Urinomas developed in three, which were drained percutaneously with complete resolution. Prior to 1985 six patients with grade II injuries underwent total or partial nephrectomy for major renal lacerations. Repair of shattered kidneys resulted in significant morbidity. Conservative management of major blunt injuries with judicious percutaneous intervention resulted in no renal loss. CONCLUSION: We believe that conservative therapy with timely percutaneous drainage of urinomas in children with major blunt renal injury, other than shattered kidney or pedicle injuries, optimizes renal preservation and minimizes secondary complications.

Adolescent↗
PubMed1993

Urolithiasis in children following augmentation cystoplasty.

Until recently urolithiasis in children following augmentation cystoplasty was an infrequently noted problem. We examined our 10-year experience and found urinary calculi to form in 52% of children and young adults undergoing augmentation cystoplasty. Calculi formed at a median interval of 24.5 months after surgery, predominantly in the lower tract. Urinary tract infection was a statistically significant risk factor, while the use of absorbable staples, intestinal mucus and hypocitraturia were also implicated. Calculus composition was primarily a mixture of apatite, struvite and ammonium urate. Bladder calculi were effectively managed endoscopically in the majority of cases without complication. Upper tract calculi presented an endourological challenge.

Adolescent↗
PubMed1993

Genitourinary malformations associated with agenesis of the corpus callosum.

Agenesis of the corpus callosum is an infrequent congenital anomaly that occurs in partial or complete forms, and is frequently associated with other craniofacial and skeletal abnormalities. An increased association with genitourinary abnormalities has not been previously defined. We reviewed the records of 22 boys and 11 girls with agenesis of the corpus callosum. Of the patients 18 had complete radiological or necroscopic evaluation and 15 had physical examinations as the sole means of evaluation. Renal anomalies were the most frequent genitourinary abnormalities identified in these children, although ureteral, genital and bladder abnormalities were also encountered. There was an exceptionally high incidence of undescended testes (23%), approximately 20-fold greater than the frequency in the normal population, possibly resulting from hypothalamic insufficiency associated with midline cranial defects. We suggest, therefore, that all patients with agenesis of the corpus callosum should be thoroughly evaluated with bladder and renal ultrasound studies to rule out any genitourinary abnormalities. Male patients with agenesis of the corpus callosum and undescended testes should undergo hypothalamic/pituitary axis testing.

Abnormalities, Multiple↗
PubMed1992

Significance of accessory ductal structures in hernia sacs.

The finding of ductal structures resembling a vas deferens during pathological examination of a hernia sac specimen has significant medical and legal implications. A method of distinguishing these accessory structures from an inadvertently transected vas has been lacking and is needed. Between July 1989 and January 1990 we examined 147 hernia sacs from 105 consecutive prepubertal and adolescent boys to determine the incidence and salient histological features distinguishing these ductal structures from a true vas deferens. Luminal diameters of the ductal structures were compared with published normal age-related established vas deferens diameters and with those measured during hernia repair in 10 of our youngest patients. Among the 147 specimens 6 hernia sacs (4.1%) contained ductal structures. We found that the mean ductal diameter (0.263 mm.) was significantly smaller than that of a normal vas deferens (0.69 to 1.5 mm.). Furthermore, the surrounding mantle of tissue of these ductal structures lacked muscle tissue when studied with Masson trichrome stain. We conclude that duct diameter and trichrome staining are simple ways of differentiating these structures from a true vas deferens.

Adolescent↗
PubMed1992

Morphological and electrophysiological changes of peripheral nerve-muscle unit in the aged rat prevented by levocarnitine acetyl.

The effects of levocarnitine acetyl on structure and function of the sciatic nerve and neuromuscular junctions of the soleus and extensor digitorum longus muscles were studied in the aged rat. To that end, neuromuscular conduction velocity (NMCV) was measured in vivo and morphological and morphometric evaluations were performed. Treatment with levocarnitine acetyl, 150 mg/kg day for six months, restored NMCV values to the levels measured in the young rat; significantly reduced the number of degenerating elements; and increased the number of myelinated fibres having normal structural features. In the soleus and extensor digitorum longus muscles, levocarnitine acetyl increased the complexity of neuromuscular junctions. These experimental findings suggest a neurotrophic action of levocarnitine acetyl on the peripheral nervous system that might have therapeutical applications in age-related peripheral nerve changes.

Acetylcarnitine↗
PubMed1992

Levocarnitine acetyl stimulates peripheral nerve regeneration and neuromuscular junction remodelling following sciatic nerve injury.

The effects of levocarnitine acetyl were investigated on both peripheral nerve regeneration and neuromuscular remodelling in male Sprague-Dawley rats, three months of age, following crush of their left sciatic nerve. Levocarnitine acetyl, 150 mg/kg/day in drinking water, was given from one week before to 5, 15, 20, and 60 days after nerve crush. The sciatic nerve was examined morphologically at all given times and morphometrically at 15, 20, and 60 days after the lesion. Morphology, at 5, 15, and 60 days, and morphometry, at 60 days after the nerve crush, were also performed on the neuromuscular junction in the soleus and extensor digitorum longus muscles. Five days after nerve crush, complete axonal degeneration was observed in both control and treated rats. At 15 and 20 days, recovery from injury in treated animals was better than in controls, as shown by a significantly higher increase in the number of regenerating axons. At the same times, denervated endplates were present in both groups. At 60 days, axonal regeneration restored the number of axons to normal values in all injured animals, while their size maturation was greater in treated rats than in controls. A markedly lower number of degenerating elements was found in treated animals. In the neuromuscular junctions of the soleus and extensor digitorum longus muscles, nerve terminal branch points were reduced in the lesioned rats in comparison with uninjured ones. However, morphometric analysis revealed a greater endplate complexity in treated animals in which, at 60 days after nerve crush, nerve terminal branching and sprouting index values were significantly higher than in controls. It is concluded that levocarnitine acetyl exerts a beneficial effect on nerve regeneration processes and synaptic remodelling in crush-induced neuropathies.

Acetylcarnitine↗
PubMed1990

Significance of intraoperative venographic patterns on the postoperative recurrence and surgical incision placement of pediatric varicoceles.

Intraoperative post-ligation spermatic venography has proved to be a reliable adjunct in pediatric varicocele surgery. In a previous study we described the technique and initial results. In this series of 60 consecutive patients with pediatric varicoceles having intraoperative venography, we specifically studied the collateral venous circulation and crossover veins to characterize the venographic patterns associated with varicocelectomy failure. The relationship of incision site and number of venograms necessary to ensure complete interruption of the internal spermatic system was evaluated to determine if an optimum incision placement exists, minimizing the number of venograms necessary. Our data indicate that the most common etiology of recurrent varicocele in children seems to be residual proximal (central) collateral veins, pelvic collateral veins (that is cremasteric, deferential and crossover veins) rarely seem to contribute to varicocelectomy failure and there is an inherent but low risk of varicocelectomy failure despite radiological evidence of complete internal spermatic vein interruption.

Adolescent↗
PubMed1990

Efficacy of orchiopexy by patient age 1 year for cryptorchidism.

We evaluated 77 male patients with true cryptorchidism ranging from 2 to 46 months old to determine whether orchiopexy could be performed safely and efficiently, and whether treatment was helpful in patients less than 1 year old. Our results indicate that orchiopexy in patients younger than 1 year is safe, effective and beneficial, and optimizes treatment of this condition.

Age Factors↗
PubMed1989

Significance of epididymal and ductal anomalies associated with testicular maldescent.

Epididymal abnormalities have long been found in conjunction with cryptorchid testicles. The aim of this study was to document the different types of epididymal and ductal anomalies in relation to the position of the cryptorchid testis and to determine their clinical significance. Exploration was performed on 187 cryptorchid testes in 174 boys. The position of the testis and the epididymal and ductal anomalies were documented at operation. A biopsy was taken from the testis or atretic spermatic cord structures for light microscopy. Epididymal, ductal and/or testicular anomalies were detected in 43 per cent of the 187 testes, including anomalies of ductal fusion, anomalies of ductal suspension and anomalies associated with absent or vanishing testes. Biopsy of the testes with severe anomalies of ductal fusion showed preservation of germ cells in 69 per cent and diminished germ cells in 31 per cent. The higher the arrest of testicular descent, the more grossly abnormal was the associated ductal system. Early successful orchiopexy alone may not ensure subsequent fertility despite the presence of normal germ cells.

Biopsy↗