Search PubMed⌕ Search

Biomedical subjects

R C Hamdy

Publications and source records attributed to R C Hamdy.

At least 37 records · Page 2Linked to original sources

Alendronate.

Explore the source record for details and available documents.

Alendronate↗

Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cells.

Hydrogen peroxide (H2O2) is a reactive oxygen species generated by several metabolic pathways in mammalian cells. Endothelial cells are extremely susceptible to oxidative stress. H2O2 has been reported to increase the permeability in these cells. Using rat heart endothelial cell culture as a model system, we examined the effect of H2O2 on the gene expression of vascular endothelial growth factor (VEGF), a potent mitogen of endothelial cells and a vascular permeability factor. By Northern blot analysis we found that VEGF mRNA responded to H2O2 in a dose-and time-dependent manner. The induction was superinduced by cycloheximide and blocked by actinomycin D. N-Acetylcysteine, a synthetic antioxidant, was able to suppress the induction. H7, a protein kinase C inhibitor, could also block the induction. Electrophoretic mobility shift assay revealed an enhanced binding of transcription factors, AP-1 and NF-kappaB. Immunoblot analysis showed that the amount of secreted VEGF was elevated in the medium 4 h after H2O2 stimulation. Our results demonstrate that VEGF gene expression is upregulated by H2O2 in these endothelial cells.

Acetylcysteine↗

Upregulation of endothelin-1 production by lysophosphatidic acid in rat aortic endothelial cells.

Addition of lysophosphatidic acid (LPA) to rat aorta-derived endothelial cells significantly induced preproendothelin-1 (preproET-1) mRNA expression. PreproET-1 mRNA levels reached a plateau within 1 h after the addition of 0.5 microM LPA and declined after 2 h. The induction was superinduced by cycloheximide and was blocked by actinomycin D. Suramin, an LPA receptor antagonist, abolished the induction of preproET-1 mRNA by LPA. Protein kinase C inhibitors, H7 and bisindolylmaleimide, were able to block the induction. Transient transfection experiment revealed that the elevated preproET-1 mRNA was a result of the activation of ET-1 gene activity. Electrophoretic mobility shift assay revealed that LPA stimulated the binding of AP-1. The secreted level of ET-1 was elevated 2.3-fold after 12 h of stimulation with LPA. Our results suggest that the upregulation of preproET-1 by LPA may serve to augment and prolong the vasoconstriction action of LPA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Upregulation of vascular endothelial growth factor by angiotensin II in rat heart endothelial cells.

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and a vascular permeability factor. In this study we found that the addition of angiotensin II (AII) to rat heart endothelial cells induced VEGF mRNA production. VEGF mRNA levels reached a plateau within 2 h after the addition of AII and decreased after 4 h. The induction was superinduced by cycloheximide and blocked by actinomycin D. Losartan, an AT1 receptor antagonist, abolished the induction of VEGF mRNA by AII, whereas PD 123319, an AT2 receptor antagonist, had no effect on VEGF mRNA induction. H7, a protein kinase C inhibitor, blocked the induction. RT-PCR experiments showed two mRNA species (VEGF 120 and VEGF 164) in these cells and both species were stimulated by AII. Transient transfection experiment showed that VEGF promoter activity was increased 2.2-fold upon AII stimulation. Electrophoretic mobility shift assay revealed an enhanced binding of transcription factors AP-1 and NF-kappa B. Immunoblot analysis showed that the amount of secreted VEGF was elevated in the medium 8 h after AII stimulation. Our results demonstrate for the first time that the upregulation of VEGF by AII may play a significant role in AII-induced hyperpermeability.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice.

Generation of free radicals upon reperfusion has been cited as one of the major causes of ischaemia/reperfusion injury. The following series of experiments was designed to study the effect of manganese superoxide dismutase (MnSOD) overexpression in transgenic mice on ischemia/reperfusion injury. A species of 1.4 kb human MnSOD mRNA was expressed, and a 325% increase in MnSOD activity was detected in the hearts of transgenic mice with no changes in the other antioxidant enzymes or heat shock proteins. Immunocytochemical study indicated an increased labeling of MnSOD mainly in the heart mitochondria of the transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x left ventricular developed pressure, was 52 +/- 4% in the transgenic hearts as compared to 31 +/- 4% in the non-transgenic hearts. This protection was accompanied by a significant decrease in lactate dehydrogenase release from the transgenic hearts. Overexpression of MnSOD limited the infarct size in vivo in a left coronary artery ligation model. Our results demonstrate that overexpression of MnSOD renders the heart more resistant to ischemia/reperfusion injury.

Animals↗

Chondrodiatasis in a patient with spondyloepimetaphyseal dysplasia using the Ilizarov technique: successful correction of an angular deformity with ensuing ossification of a large metaphyseal lesion. A case report.

Distraction through the physis (chondrodiatasis) is a controversial technique with unpredictable results. However, it has been used in the past for the lengthening and correction of angular deformities of long bones. We report the case of an 11-year-old patient with spondyloepimetaphyseal dysplasia (SEMD) who presented with a severe recurvatum deformity of the left proximal tibia secondary to collapse of the tibial plateau into a large metaphyseal cystic lesion. Using the chondrodiatasis technique with a percutaneously applied Ilizarov circular frame, we were able to correct this deformity. Surprisingly, healing and ossification of the metaphyseal lesion was simultaneously observed at the end of the treatment, a finding which, to the best of our knowledge, has not been previously reported.

Bone Cysts↗

Nandrolone decanoate for men with osteoporosis.

To compare the efficacy and safety of nandrolone decanoate and calcium (NDC) with those of calcium alone (CAL) in men with idiopathic osteoporosis, a 12-month, randomized, prospective, controlled study, was performed in an outpatient clinic. Twenty-one men with idiopathic osteoporosis (as determined by radiological and dual energy x-ray absorptiometry findings) were randomly allocated to either 50 mg nandrolone decanoate intramuscularly (im) weekly and 1,000 mg oral calcium carbonate daily (NDC group) or to 1,000 mg oral calcium carbonate daily (CAL group). Bone densitometry (total body, left femur, and lumbar spine), serum, and urine biochemical parameters were measured at 3-month intervals. In the NDC group, bone mineral density initially increased, reached a plateau, and then decreased to near baseline levels at 12 months. Increases in lean muscle mass mirrored these changes. Free and total testosterone significantly decreased. Hemoglobin increased in all patients in this group. Patients in the CAL group exhibited no significant change in either total body or bone mineral density or biochemical parameters. Thus, nandrolone decanoate, 50 mg im weekly, transiently increases the bone mass of men with idiopathic osteoporosis in this preliminary study. Careful monitoring is necessary.

Absorptiometry, Photon↗

Complications of limb-lengthening in children who have an underlying bone disorder.

We retrospectively reviewed the results, particularly with regard to complications, of lengthening of long bones in eight children (nine limb segments) who had a limb-length discrepancy secondary to an underlying bone disorder (Group 1). The mean age of these patients was twelve years (range, six to sixteen years), the mean preoperative limb-length discrepancy was 6.0 centimeters (range, 2.7 to 8.8 centimeters), and the mean lengthening of the nine limb segments was 6.2 centimeters (range, 2.7 to 9.0 centimeters). Only two extremities were equalized. We compared the results in Group 1 with those of limb-lengthening in seven children (nine limb segments) who had a discrepancy secondary to post-traumatic growth arrest (Group 2) and seven children (seven limb segments) who had a discrepancy secondary to growth arrest following an infection in the bone (Group 3). All of the procedures were performed at our institution during the same time-period by the same surgeons. There were forty-one complications (twenty-five minor and sixteen major), with a mean of five complications per limb segment, in Group 1; twenty-six complications (twenty minor and six major), with a mean of three complications per limb segment, in Group 2; and twenty-two complications (fourteen minor and eight major), with a mean of three complications per limb segment, in Group 3. The results in Group 1 suggest that the Ilizarov technique for lengthening, although effective in restoring the length of the extremity, is associated with a higher rate of complications in patients who have a discrepancy due to an underlying bone disorder than in those who have a discrepancy due to growth arrest. Therefore, caution should be exercised before a lengthening procedure is recommended for a patient who has an underlying bone disorder.

Adolescent↗

Regulation of thrombospondin-1 production by angiotensin II in rat heart endothelial cells.

Thrombospondin-1 (TSP-1) is synthesized, secreted, and incorporated into the extracellular matrix by a variety of cells, including the endothelial cells. Addition of angiotensin II (AII) significantly induced TSP-1 mRNA in rat heart-derived endothelial cells. TSP-1 mRNA levels reached a plateau within 2 h after the addition of AII and decreased after 5 h. The induction was superinduced by cycloheximide and blocked by actinomycin D. Losartan, an AT1 receptor antagonist, could abolish the induction of TSP-1 mRNA by AII. Phorbol 12-myristate 13-acetate (TPA) was found to enhance TSP-1 mRNA level whereas a protein kinase C inhibitor, H7, was shown to block the induction. Immunoblot analysis revealed that TSP-1 was detectable in the medium 4 h after AII stimulation. Our results suggest that the upregulation of TSP-1 by AII represents an important mechanism leading to perivascular fibrosis in the heart.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Use of emergency departments by the elderly in rural areas.

Sparse information is available concerning use of emergency departments (EDs) by the elderly in rural areas. We reviewed records of all patients seeking care at EDs of three rural hospitals during 7 days in October 1991. We found that elderly people did not use EDs in proportion to their numbers in the community (15.2% versus 19.3%). Compared with younger ED patients, more elderly patients required an ambulance (40.8% versus 10.7%), more needed hospitalization (38.4% versus 11.9%), and their ED stays were longer (140 minutes versus 89 minutes). Falls/injuries (18.7%) and cardiac illness (18.1%) were the most frequent reasons for ED visits by the elderly, and relatively few (2.8%) had confusion. More elderly patients arrived during daytime hours than during the night, and more on weekends than weekdays. Also, we found no difference between patients in the 65- to 74-year-old age group and those aged 75 years and older.

Accidental Falls↗

Factors influencing the accuracy of home blood pressure measurement.

BACKGROUND: Hypertension is a common disorder, affecting approximately 50 million Americans. Because many people have this disorder and its sequela, it is important not only to detect hypertension but also to monitor adequacy of control. Over the past few years, blood pressure monitoring devices (BPMDs) have become available for individuals to measure their blood pressure (BP) in the convenience of their home. These instruments are touted as being accurate. METHODS: We conducted a study with volunteers who use BPMDs to see how they are used and to assess their accuracy. A BP reading was considered accurate if the differences between the volunteers' and technicians' systolic and diastolic readings were both 10 mm Hg or less. RESULTS: Of 91 patients, 31 (34%) obtained inaccurate readings. The inaccuracy could not be attributed to the type of the instrument, the cost of the instrument, the educational level of the user, or the age of the instrument. CONCLUSIONS: This study shows, despite other studies purporting accuracy, that a significant number of inaccurate readings are obtained by patients using BPMDs. Supervision of their use needs to be incorporated into the physician follow-up to ensure that there is a reasonable correlation between values obtained using the mercury sphygmomanometer and the BPMD.

Adult↗

Management of fibular hemimelia: amputation or limb lengthening.

We reviewed retrospectively 22 patients (23 limb segments) with fibular hemimelia treated by amputation or limb lengthening to evaluate these methods of treatment. There were 12 boys and 10 girls, all with associated anomalies in the lower limbs. Twelve patients (13 limb segments) had early amputation and prosthetic fitting and ten had tibial lengthening using the Ilizarov technique. At the latest follow-up, the twelve patients who had amputation were functioning well and had few complications. The ten patients who had lengthening had suffered numerous complications, and all had needed either further corrective surgery or to wear braces or shoe-raises. Two of the ten lengthened limbs required late amputation for poor function or cosmesis. There were fewer hospital admissions, clinic visits, and periods of absence from school in the amputation group. Our findings suggest that amputation is a more effective method of management than limb-lengthening in severe fibular hemimelia. The Ilizarov method is an attractive alternative for selected patients, but its exact role is not yet established. One problem is that families often have unrealistic expectations of the surgical and prosthetic technology available and may refuse amputation when this has been recommended.

Amputation, Surgical↗

[Histologic evaluation of bone regeneration in cases of limb lengthening by Ilizarov's technique. An experimental study in the dog].

The histology of bone regeneration in cases of limb lengthening was studied in eight adult dogs. Following an osteotomy of the right fibula, an Orthofix (four dogs) or an Ilizarov external fixator (4 dogs) was installed and an osteotomy of the right tibia performed. Lengthening was started seven days after the surgery at the rate and rhythm of 0.5 mm every 12 hours for three weeks and was then followed by compression of 1 mm. The animals were then sacrificed in pairs 3, 6, 9 and 12 weeks after the start of lengthening. Histological evaluation of regenerate bone was performed using hematoxylin and eosin, trichrome and Von Kossa stain (decalcified). New bone at the site of distraction seemed to be formed mostly through intramembranous, and to a lesser extent, through endochondral ossification as evident by the presence of cartilaginous islands within the distraction gap of old specimens. However, these foci of cartilage cells did not have the appearance of growth plates. From the third week of lengthening, collagen fibers were laid down along the longitudinal axis of distraction. Mineralization of these fibers started at the bone ends and during the following weeks, progressed towards the center of the distraction gap. New bone was formed from both the medullary cavity and the periosteum.

Animals↗

Regulation of endothelin-1 production by a thromboxane A2 mimetic in rat heart smooth muscle cells.

Thromboxane A2 (TXA2) and ET-1 have been known to play important roles in modulating vascular contraction and growth. The present study was undertaken to examine the effect of TXA2 on the induction of endothelin-1 (ET-1) mRNA and protein levels in smooth muscle cells derived from rat heart. U-46619, a stable TXA2 mimetic, superinduced preproET-1 mRNA in the presence of cycloheximide in these cells. This effect could be blocked by SQ-29548, a TXA2/prostaglandin H2 receptor antagonist and by actinomycin D, and RNA synthesis inhibitor. In addition, H7, a protein kinase C inhibitor, could abolish the induction. Transient transfection experiment revealed that the elevated ET-1 mRNA level after U-46619 treatment was a result of the activation of ET-1 gene activity. The elevated ET-1 message level was accompanied by increased ET-1 release into the cultured medium. These results show that the short-lived TXA2 can induce potent and long-lived ET-1. These findings support a potential role for ET-1 in the pathogenesis of coronary atherosclerosis and hypertension evoked by TXA2.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Angiotensin II induces TIMP-1 production in rat heart endothelial cells.

Angiotensin II (AII) was found to upregulate tissue inhibitor of metalloproteineses-1 (TIMP-1) gene expression in rat heart endothelial cells in a dose and time-dependent manner. The maximal stimulation of TIMP-1 mRNA was achieved by 2 h after the addition of AII. This effect was blocked by losartan, an AT1 receptor antagonist and by calphostin C, a protein kinase C inhibitor. Addition of cycloheximide superinduced and actinomycin D abolished the induction. These results suggest that AII stimulates TIMP-1 production by a protein kinase C dependent pathway which is dependent upon de novo RNA synthesis. Immunoprecipitation experiment showed an enhanced band of 28 kDa from the conditioned medium of AII-treated cultures. Immunoblot analysis revealed that TIMP-1 was detectable in the conditioned medium 4 h after AII stimulation. Since endothelial cells line the blood vessels and sense the rise in AII associated with hypertension, the TIMP-1 released by these cells may provide an initial trigger leading to cardiac fibrosis in angiotensin-renin dependent hypertension.

Angiotensin II↗