Discovery of dual-target natural antimalarial agents against DHODH and PMT of Plasmodium falciparum: pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.

Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two P. falciparum enzymes; P. falciparum Dihydroorotate dehydrogenase (PfDHODH) and P. falciparum phosphoethanolamine methyltransferase (PfPMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against PfDHODH. Following this, 1201 natural compounds with docking scores of ≤ -7 kcal/mol were docked into the active site of the second enzyme PMT. The top nine compounds were subjected to further investigation using MM-GBSA free binding energy calculations and ADME analysis. The results revealed favourable free binding energy values better than the references, as well as acceptable pharmacokinetic properties. Compounds ZINC000013377887, ZINC000015113777, and ZINC000085595753 were scrutinized to assess their interaction stability with the PfDHODH enzyme, and chemical stability reactivity using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. These findings indicate that the three natural compounds are potential candidates for dual PfDHODH and PfPMT inhibitors for malaria treatment.

A novel technique for modified B-Lynch suture for the control of atonic postpartum haemorrhage.

The B-Lynch brace suture technique is a life-saving procedure. It is a simple and safe alternative to hysterectomy. Thus, it preserves fertility with less surgical morbidity. In this case series, we evaluated the use of a novel modification of the B-Lynch brace suture to minimise its potential reported complications. Five women with intractable primary atonic postpartum haemorrhage were reported. They were initially managed with bilateral uterine artery ligation. The procedure was resorted to women who did not respond to ligation. The procedure is efficient. Women were followed up for up to 24 months to report any complications.

The use of multiple 8 compression suturing as a novel procedure to preserve fertility in patients with placenta accreta: case series.

Placenta accreta/percreta is a serious cause of intractable post-partum haemorrhage during caesarean section and a common cause of peripartum hysterectomy. In this case series, we evaluated the use of multiple 8 sutures as a novel procedure to preserve the uterus in these cases. Seven women with placenta accreta/percreta were initially managed with bilateral uterine artery ligation. The procedure was resorted to in cases that did not respond to ligation (five women). Women were followed up for up to 24 months to report complications.

Gastrointestinal quality of life in patients after anti reflux surgery.

A subset of patients does not report improvement of symptoms or satisfaction after antireflux surgery. The aim of this study is to assess the effect of pre-existing depression as a factor in patient satisfaction and gastrointestinal quality of life index (GIQLI) outcomes after antireflux surgery. Patients undergoing antireflux surgery who had filled a preoperative quality of life score and had more than 1 year follow-up were included in this study. Based on available history and self-reported medication use, patients were divided in two groups: with depression (group A) and without depression (group B). Fifty-four patients with completed preoperative GIQLI questionnaire were contacted for this study; 32 (59%) patients completed the postoperative questionnaire. Seven patients (22%) had psychological disorder (group A) in the form of depression The GIQLI in groups A and B increased significantly from 64.4 +/- 17.3 and 89.6 +/- 18.6 to 88.6 +/- 23.7 (P < 0.001) and 102.2 +/- 18.6 (P = 0.02), respectively, after the surgery. There was significant improvement in the quality of life in patients after antireflux surgery based on the GIQLI assessment. This improvement was also reported in patients with history of depression.

Treatment of urethral stones by retrograde manipulation and extracorporeal shock wave lithotripsy.

OBJECTIVE: To assess the effect of retrograde manipulation and extracorporeal shock wave lithotripsy (ESWL) as a monotherapy for urethral stones that are not associated with urethral strictures. PATIENTS AND METHODS: Between August 1993 and January 1995, 34 male patients (mean age 38.7 years, range 7-55) presented with urethral stones. No patient had a suggested or past history of urethral stricture. Lidocaine jelly (2%) was instilled and retained inside the urethra for 5 min. A 16 F urethral catheter was advanced gently to push the stone back to the urinary bladder. Twenty patients had ESWL of their stones in the bladder, using a Storz Modulith SL20, in the prone position. Tilting the patient about 15 degrees towards the side with the stone minimized movement of the stone during fragmentation. In-line co-axial echography (3.5 MHz) and intermittent pulsed fluoroscopy were used to monitor stone fragmentation. In situ fragmentation of posterior urethral stones was not possible because localization was difficult and the treatment was painful. Thirteen patients had cysto-urethroscopy and mechanical cystolitholapaxy under general anaesthesia. RESULTS: Stones impacted in the posterior urethra in 31 (91%) patients and in the anterior urethra in three (9%) patients. Stones ranged in size from 7 to 25 mm. One patient expelled an anterior urethral stone after the instillation of 2% lidocaine jelly. The urethral stones were pushed back to the bladder without complication in the remaining 33 patients. All 20 patients except one had their stones fragmented by ESWL in one session. The mean number of shock waves was 3600 +/- 1480 (range 1200-6000) and the generator voltage ranged between 5 kV (560 bar) to 8 kV (940 bar). No patient in the ESWL group required anaesthesia or analgesia. Thirteen patients had successful mechanical cystolitholapaxy with no complications. CONCLUSION: Both endoscopic lithotripsy and ESWL of urethral stones are safe and effective. However, transurethral lithotripsy requires general anaesthesia and carries a risk of bladder and urethral trauma. This study demonstrated that, in the absence of urethral stricture, urethral stones can be pushed back safely to the urinary bladder and fragmented effectively by ESWL. The success of the treatment depends on adequate anaesthesia of the urethra before inserting the urethral catheter. We propose that this new technique should be considered before resorting to endoscopic or surgical management of urethral stones, particularly in children.

Treatment of renal colic by desmopressin intranasal spray and diclofenac sodium.

The vasopressin analogue, 1-desamino-8-arginine vasopressin (desmopressin), is a potent antidiuretic without the pressor effects of vasopressin. A total of 18 patients with acute renal colic due to stone disease received 40 microgramsf1p4mopressin intranasal spray with encouraging results. There was a significant decrease in the colic pain intensity from an initial mean visual analogue score of 67 +/- 17 mm. to 39 +/- 36 mm. within 30 minutes (p < 0.001). Eight patients (44.4%) had complete pain relief within 30 minutes of administering intranasal desmopressin spray. Nine of 10 patients who required intramuscular diclofenac sodium achieved complete pain relief within another 30 minutes. In other words, when intranasal desmopressin spray was administered before diclofenac sodium, 94.4% of the patients achieved complete pain relief and were discharged home. The mechanism of analgesic action of desmopressin in renal colic is uncertain. At the peripheral level, desmopressin may alleviate the acute renal colic through its potent antidiuretic effect or by relaxing the renal pelvic and ureteral smooth muscles. The central analgesic effect of desmopressin by stimulating the release of the hypothalamic beta-endorphin is proposed. We conclude that intranasal desmopressin spray can be used successfully in the treatment of renal colic. It may also replace prostaglandin synthetase inhibitors in treating renal colic with the advantage of avoiding the potential side effects. Further studies are needed to investigate whether the combination of desmopressin with analgesics or spasmolytic drugs offers competitive results compared with those achieved by prostaglandin synthetase inhibitors in the treatment of renal colic.

Proposed new method for nonoperative treatment of urethral stones.

Urethral calculi is a common clinical problem in the Middle and Far East. Different endoscopic and operative techniques have been used in the treatment of impacted urethral stones. We report a noninvasive procedure to treat this condition. Intraurethral instillation of 2% lidocaine jelly was followed by spontaneous expulsion of the stone in 14 of 18 patients. The indications and limitations of the method are outlined.

Management of fracture of the penis in Qatar.

We present 21 patients with fracture of the penis treated between July 1982 and July 1990. Eighteen patients were treated surgically, with good functional and morphological recovery; 3 refused surgery, 1 of whom had penile deformity and pain on erection. The literature is reviewed with respect to the necessity of different diagnostic and therapeutic options.

Treatment of renal colic by prostaglandin synthetase inhibitors and avafortan (analgesic antispasmodic).

In a study of the pain-relieving effect of 3 drugs commonly used to treat acute renal colic in this hospital, intravenous indomethacin and intramuscular diclofenac (prostaglandin synthetase inhibitors) were compared with intravenous Avafortan (analgesic antispasmodic). As first-line analgesics, prostaglandin synthetase inhibitors, if given intravenously, offer an effective alternative to Avafortan. Of 145 patients studied, 32 required a second injection for complete relief of pain. Administering a second dose of prostaglandin synthetase inhibitors resulted in equally significant pain relief rate even though the route was intramuscular.