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Biomedical subjects

R Raina

Publications and source records attributed to R Raina.

At least 19 recordsLinked to original sources
PubMed2006

Early combination therapy: intracavernosal injections and sildenafil following radical prostatectomy increases sexual activity and the return of natural erections.

Early pharmacological prophylaxis has been reported to increase the return of spontaneous erections following radical prostatectomy (RP). In this study, we evaluated the role of intracavernosal alprostadil (PGE1) combined with sildenafil in stimulating early recovery of spontaneous erections following RP. In this prospective study, we included 22 patients who underwent bilateral nerve-sparing RP after October 2004. Sildenafil dose of 50 mg/day was started at the time of hospital discharge. Of 22 patients, 18 started on PGE1-4 microg (1-8) and four started on low-dose Trimix (20 U) 2-3 times/week. These patients are followed up at regular intervals (3, 6, 9 and 12 months) with abridged version of the International Index for Erectile Function-5 questionnaire. Patient compliance, return of sexual activity and return of natural erection, adverse effects and reasons for discontinuation were recorded. Penile doppler studies were performed during followup visits to assess the vascular status. After a mean followup of 6 months (3-8 months), 11/22 (50%) patients had return of spontaneous partial erections. Of the 18 PGE1 users, six continued 4 microg PGE1, four increased the dose to 8 microg, six decreased the dose to 2 microg and two patients further reduced the dose to 1 microg. Of four low-dose Trimix users, three increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients, 21 were sexually active: 12/21 (57%) with the injections alone and 9/21 (42.9%) with combination therapy (injections (PGE1) and sildenafil). Penile doppler studies revealed arterial insufficiency in 77% (17/22) patients and venous insufficiency in one patient. Early intracavernosal injections following RP facilitated early sexual intercourse, patient satisfaction and potentially earlier return of natural erections. Early combination therapy with sildenafil allowed a lower dose of intracavernous injections, minimizing the penile discomfort.

Alprostadil↗
PubMed2005

Role of nitric oxide in ovarian follicular development and egg production in Japanese quail (Coturnix coturnix japonica).

Role of nitric oxide (NO) in regulating the reproductive functions at hypothalamo-hypophysealovarian axis in Japanese quail was studied. In first experiment, metabolites of NO, i.e. nitrite and nitrate (NO2 and NO3) were estimated together in hypothalamus, serum and ovarian follicles of good and poor layers. In the second experiment, different NO modulators such as L-arginine (L-Arg), sodium nitroprusside (SNP) and N(G)-nitro-L-arginine methyl ester, HCl (L-NAME) were administered to the birds. In the first experiment, significantly higher (P < 0.01) NO2 and NO3 levels in serum, hypothalamus and largest (F1) ovarian follicles were observed in good layers as compared to poor layers. Higher (P < 0.05) NO2 and NO3 concentration was observed in F1 follicles than smaller follicles (F2) only in good layers. The NO2 and NO3 concentration was significantly reduced (P < 0.05) in post ovulatory follicles (POFs) in comparison to F1 and F2 follicles. In the second experiment, the serum NO2 and NO3 concentrations were higher (P < 0.05) in the SNP, lower (P < 0.05) in the L-Name group and unchanged in the L-Arg treated group in comparison to control group. compared to control, L-Arg and SNP increased (P < 0.05) the hypothalamic NO2 and NO3 concentration where as L-NAME reduced (P < 0.05) these levels. The NO2 and NO3 concentration was increased (P < 0.05) as the follicle size increased and it was significantly reduced (P < 0.05) in POFs. The higher (P < 0.05) follicular NO2 and NO3 concentration was observed in L-Arg group in comparison to control group. Egg production was also found to be higher (P < 0.05) in L-Arg group whereas it was not different (P > 0.05) in SNP and L-NAME treated groups. The yolk weight and yolk to albumin ratio was reduced (P < 0.05) in L-NAME group in comparison to control group. It may be concluded from the present study that NO plays a key role in regulating follicular development, ovulatory mechanisms and egg production in Japanese quail.

Animals↗
PubMed2004

Sildenafil citrate vs intracavernous alprostadil for patients with arteriogenic erectile dysfunction: a randomised placebo controlled study.

We compared the effectiveness of sildenafil citrate and alprostadil in improving arterial penile inflow (peak systolic velocity (PSV)) and penile rigidity in 55 patients with erectile dysfunction caused by atherosclerosis. A total of 35 patients with pure vasculogenic impotency were randomly assigned to alprostadil (Av group; n=11), sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20 patients with nonvasculogenic impotency were randomly assigned to alprostadil (A group; n=10) or Sildenafil (S group; n=10): Av and A used alprostadil injection (capable of giving a full erection) once a week for 1 month, Sv and S took daily oral sildenafil (25 mg) for 1 month, and P took daily oral placebo for one month. The PSV was measured with Duplex sonography and penile rigidity was assessed using the IIEF-15 questionnaire, both of which were administered before and after treatment. Although both treatments improved penile rigidity, they increased PSV only in the Av and Sv groups. Our results suggest that alprostadil and oral therapy should be the starting therapy in men with vasculogenic impotency, whereas alprostadil should be avoided as the first-line approach in men with nonvasculogenic impotency.

Adult↗
PubMed2003

Long-term efficacy and compliance of intracorporeal (IC) injection for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis.

Baseline and follow-up data from 102 patients using intracorporeal (IC) injection for erectile dysfunction (ED) following RP were retrospectively collected. We compared baseline International Index for Erectile Function (IIEF) questionnaires with the abridged IIEF-5 questionnaires, referred to as the Sexual Health Inventory of Men (SHIM) to determine drug efficacy. The mean presurgery SHIM score was 21.75+/-5.23, which decreased to 4.23+/-3.48 after surgery and increased to 19.46+/-8.78 post-treatment. Overall, 68% (69/102) of patients achieved and maintained erections sufficient for sexual intercourse and 48% (49/102) of patients continued long-term therapy with a mean use of 3.7+/-1.9 y. In all, 52% (53/102) patients discontinued IC therapy. However when excluding patients who switched to oral therapy, had loss of partner or return of normal erections; the compliance to IC injections was 70.6% (71/102). There was no difference in the SHIM analysis between the nerve sparing (NS) and the non-NS or between the types of medications used. IC injections can provide excellent long-term efficacy and compliance in up to 70% of the patients. This study suggests that IC injections are an excellent salvage option in NS patients who fail oral therapy and a first option in patients with non-NS procedures.

Aged↗
PubMed2001

Management of erectile dysfunction following radical prostatectomy.

Radical prostatectomy is the standard treatment for organ/specimen-confined prostate cancer, yet erectile dysfunction in selected series is still reported as high as 90% after this procedure. Thus, most men need adjuvant treatments to be sexually active following radical prostatectomy. These include vacuum constriction devices, intracorporeal injections of vasoactive drugs, and transurethral dilators, all of which have reported response rates of 50% to 70%. Unfortunately, long-term compliance is suboptimal, with a discontinuation rate of nearly 50% at one year. These non-oral options should be offered on an individual basis to patients who have failed oral therapy since efficacy and compliance vary. Also, these options should be considered in the early postoperative period to enhance sexual activity and penile oxygenation, which may prevent corporeal fibrosis. Early penile rehabilitation with intracavernosal injections or vacuum constriction devices should be encouraged to increase chances for recovery of rigid erections. In patients with some preservation of nerve tissue, oral sildenafil may be effective in promoting an earlier return of erectile function. The potential impact of sildenafil and other new oral therapies should encourage urologists to continue to perform and perfect the nerve-sparing approach.

Erectile Dysfunction↗
PubMed2000

Comparative electrocardiographic studies, and differing effects of pentazocine on ECG, heart and respiratory rates in young sheep and goats.

The effects of pentazocine on electrocardiogram (ECG) heart and respiratory rates were studied in young sheep and goats as a prelude to its clinical use as an opioid analgesic in the two species. The ECG was monitored by standard bipolar leads that provided discernible electrocardiographic features only in Lead I. Electrocardiograms of lambs differ significantly from those of kids with respect to QRS complex, P-R interval and T wave. Higher basal heart rate in lambs is apparently due to shorter P-R interval and shorter interval between successive cardiac cycles (p<0.05). Pentazocine, 3mgkg(-1) i.m., appears safer for lambs than kids as it significantly decreased P-R interval, Q-T interval, cardiac cycle duration, interval between successive cardiac cycles, respiration rate, and increased heart rate in kids but not in lambs (p<0.05).

Journal Article↗
PubMed1999

Negative effect of the 5'-untranslated leader sequence on Ac transposon promoter expression.

Transposable elements are used in heterologous plant hosts to clone genes by insertional mutagenesis. The Activator (Ac) transposable element has been cloned from maize, and introduced into a variety of plants. However, differences in regulation and transposition frequency have been observed between different host plants. The cause of this variability is still unknown. To better understand the activity of the Ac element, we analyzed the Ac promoter region and its 5'-untranslated leader sequence (5' UTL). Transient assays in tobacco NT1 suspension cells showed that the Ac promoter is a weak promoter and its activity was localized by deletion analyses. The data presented here indicate that the core of the Ac promoter is contained within 153 bp fragment upstream to transcription start sites. An important inhibitory effect (80%) due to the presence of the 5' UTL was found on the expression of LUC reporter gene. Here we demonstrate that the presence of the 5' UTL in the constructs reduces the expression driven by either strong or weak promoters.

DNA Transposable Elements↗
PubMed1998

Concerted formation of macromolecular Suppressor-mutator transposition complexes.

Transposition of the maize Suppressor-mutator (Spm) transposon requires two element-encoded proteins, TnpA and TnpD. Although there are multiple TnpA binding sites near each element end, binding of TnpA to DNA is not cooperative, and the binding affinity is not markedly affected by the number of binding sites per DNA fragment. However, intermolecular complexes form cooperatively between DNA fragments with three or more TnpA binding sites. TnpD, itself not a sequence-specific DNA-binding protein, binds to TnpA and stabilizes the TnpA-DNA complex. The high redundancy of TnpA binding sites at both element ends and the protein-protein interactions between DNA-bound TnpA complexes and between these and TnpD imply a concerted transition of the element from a linear to a protein crosslinked transposition complex within a very narrow protein concentration range.

Base Sequence↗
PubMed1998

Characterization of a spontaneous mutant of Azotobacter vinelandii in which vanadium-dependent nitrogen fixation is not inhibited by molybdenum.

A spontaneous mutant derivative of Azotobacter vinelandii CA12 (delta nif HDK), which vanadium-dependent nitrogen fixation is not inhibited by molybdenum (A. vinelandii CARR), grows profusely on BNF-agar containing 1 microM Na2MoO4, alone or supplemented with 1 microM V2O5. The expression of A. vinelandii vnfH::lacZ and vnfA::lacZ fusions in A. vinelandii CARR was not inhibited by 1 mM Na2MoO4, whereas molybdenum at much lower concentration inhibited the expression of vnfH::lacZ and vnfA::lacZ fusions in A. vinlandii CA12. The mutant also exhibited normal acetylene reduction activity in the presence of 1 microM Na2MoO4. The expression of A. vinelandii nifH::lacZ fusion in A. vinelandii CARR was low even though the cells were cultured under non-repressing conditions with urea as nitrogen source in the presence of Na2MoO4. The molybdenum content of A. vinelandii CARR cells was found to be about one-fourth that of A. vinelandii CA12. No nitrate reductase activity could be detected in A. vinelandii CARR when the cells were cultured in the presence of 10 microM Na2MoO4, whereas A. vinelandii CA12 exhibited some activity even with 100 pM Na2MoO4.

Acetylene↗
PubMed1998

Epigenetic mechanisms in the regulation of the maize Suppressor-mutator transposon.

Transcription and transposition of the maize Suppressor-mutator (Spm) transposon are epigenetically controlled. Methylation of specific element sequences prevents transcription and transposition in a heritable manner. Reactivation and demethylation occur in the presence of an active element, implying the existence of an element-encoded epigenetic activator. The methylation target sequences are the 0.2 kb promoter and an 0.35 kb GC-rich downstream sequence. Two Spm-encoded proteins, TnpA and TnpD, participate in transposition. In addition, TnpA has positive and negative regulatory activities. TnpA represses and activates the unmethylated and methylated Spm promoters, respectively, and it participates in the transient and heritable demethylation of the promoter and GC-rich region. There is evidence that TnpA-mediated repressor and epigenetic activator functions occur by different molecular mechanisms.

DNA Transposable Elements↗
PubMed1998

Analysis of upstream activation of the vnfH promoter of Azotobacter vinelandii.

BAL-31 deletion products of the DNA fragment containing the vnfH promoter and upstream region, when cloned in a transcriptional fusion vector and analyzed for vnfH expression in Azotobacter vinelandii, revealed that the upstream activator sequence of the vnfH promoter lies about 140 nucleotides upstream of the promoter. Subsequent substitution and deletion analysis by oligonucleotide-directed mutagenesis in the upstream region of the vnfH promoter showed that sequences 5'-GTACCATGCGGAAC-3' and 5'-GTACCTGCGGGTAC-3', located 170 and 140 nucleotides upstream of the vnfH promoter, respectively, are both required for vnfH expression. Addition of four nucleotides in the intervening sequence between the vnfH promoter and the putative VnfA (analog of NifA of the conventional molybdenum-dependent nitrogen-fixation pathway) binding site resulted in a drastic reduction of expression from the vnfH promoter in Azotobacter vinelandii, whereas addition of 10 nucleotides in the intervening sequence did not affect the expression. Therefore, the face of the helix-dependent contact appeared to be important. DNA bending seemed to play a crucial role in expression from vnfH promoter. The intervening sequence exhibited characteristics of sequence-dependent intrinsically curved DNA, as shown by anomalous low gel mobility with polyacrylamide gel electrophoresis, electron microscopy, and computer simulated curvature analysis. Distamycin at very low concentrations significantly reduced the anomaly in electrophoretic mobility of the intervening DNA sequence.

Artificial Gene Fusion↗
PubMed1996

A highly sensitive plant hybrid protein assay system based on the Spm promoter and TnpA protein for detection and analysis of transcription activation domains.

TnpA is a multifunctional DNA binding protein encoded by the maize Suppressor-mutator (Spm) transposable element. TnpA is required for transposition and is a repressor of the unmethylated Spm promoter. While analyzing protein domains using a yeast GAL4-based hybrid system in transiently transformed tobacco cells, we found that TnpA represses the > 10-fold transcriptional activation observed when the GAL4 DNA-binding domain is used alone. By contrast, compared to the backgroundless TnpA DNA-binding domain alone, 33- to 45-fold activation of the Spm promoter was observed when the VP16 activation domain was fused to it. TnpA-binding sites, but no TATA box, were required for transcription activation. Among the TnpA deletion derivatives tested, those retaining the coding sequences for the DNA-binding and protein dimerization domains gave the highest level of transcription activation when fused with the VP16 activation domain. The TnpA gene and TnpA-binding sites in the short Spm promoter therefore provide a novel, highly sensitive single-hybrid system for identifying and studying plant transcription activation domains in plant cells.

DNA Transposable Elements↗
PubMed1995

Epigenetic regulation of the maize Spm transposon.

Expression and transposition of the Suppressor-mutator (Spm) transposon of maize are controlled by interacting epigenetic and autoregulatory mechanisms. Methylation of critical element sequences prevents both transcription and transposition, heritably inactivating the element. The promoter, comprising the terminal 0.2 kb of the element, and a 0.35-kb, highly GC-rich, downstream sequence are the methylation target sequences. The element encodes two proteins necessary for transposition, TnpA and TnpD. There are multiple TnpA binding sites, both in the 5' terminal promoter region and at the element's 3' end. In addition to its role in transposition, TnpA is both a positive and a negative regulator of transcription. TnpA represses the element's promoter when it is not methylated. When the element is inactive and its promoter methylated, TnpA activates the methylated promoter and facilitates both its transient and heritable demethylation.

Base Sequence↗
PubMed1994

Epigenetic regulation of the maize Spm transposable element: novel activation of a methylated promoter by TnpA.

Spm is epigenetically inactivated by C-methylation near its transcription start site. We have investigated the interaction between TnpA, an autoregulatory protein that can reactivate a silent Spm, and the promoter of the element. The promoter undergoes rapid de novo methylation and inactivation in stably transformed plants, but only if it includes a GC-rich sequence down-stream of the promoter. TnpA activates the inactive, methylated promoter and leads to reduced methylation. By contrast, TnpA represses the active, unmethylated Spm promoter. Only the internal DNA-binding and dimerization domains of the protein are required for repression, while activation requires an additional C-terminal sequence. TnpA is therefore a unique regulatory protein with a conventional transcriptional repressor activity and a novel ability to activate a methylated, inactive promoter.

Base Sequence↗
PubMed1993

Maize Spm transposable element has an enhancer-insensitive promoter.

We have used a transient assay system to investigate the promoter region of the maize Suppressor-mutator (Spm) transposable element. All of the sequence required for constitutive promoter activity is confined to the 0.2-kb sequence upstream from the transcription start site of the element at nt 209 and designated the upstream control region. The element's promoter is weak, lacks a conventional TATA box, and depends on the presence of multiple, short repetitive sequence elements. The Spm promoter is quite insensitive to the enhancer sequence of the cauliflower mosaic virus 35S promoter. Enhancer sensitivity can be restored by providing a -30 TATA sequence and removing the G + C-rich sequence encoding the untranslated leader of the element, designated the downstream control region. Although the downstream control region is without effect on Spm promoter activity, it completely inhibits the 35S core promoter and markedly inhibits activity of the complete 35S promoter. The properties of the Spm element's promoter buffer it from both mutational and position-dependent changes in activity. We suggest that the inherent characteristics of the promoter are part of the genetic mechanism that controls the element's transposition frequency, ensuring it remains low and insertion-site independent.

Base Sequence↗