Editorial

Potentials for Use of Medicinal Plants in Female Reproductive Disorders – The Way Forwar

Ex-Vivo Uterine Activity of Theobroma Cacao (Malvaceae) Aqueous Seed Extract and Cymbopogon Citratus (Poaceae) Aqueous Leaf Extract - A Preliminary Investigation

There is a need to develop new drugs from natural products for the safe and effective management of female reproductive disorders. This research was therefore aimed at the investigation of two commonly consumed natural products on uterine function. The ex vivo uterine activity of Theobroma cacao aqueous seed extract and Cymbopogon citratus aqueous leaf extract was investigated on non pregnant mouse uteri. The effect of T. cacao (0.1 mg/mL) and C. citratus (0.1 mg/mL) on spontaneous uterine contractility and in the presence of oxytocin (11.54 nM) was examined. This study showed that T. cacao elicited a significant increase (p < 0.05) in the amplitude of spontaneous uterine contractions with no significant ch ange in the frequency, which was similarly observed with C. citratus leaf extract. An increase in amplitude and frequency of oxytocin induced uterine  contractions was observed in the presence of T. cacao while with C. citratus there was a significant (p< 0.05) reduction in amplitude and non significant reduction in frequency of oxytocin induced uterine contractions. The uterotonic effect of both extracts in the absence of agonists observed maybe as a result of constituents with agonistic activity on intra cellular calcium. This study has shown that T. cacao and C. citratus could stimulate uterine activity and may therefore be useful in the management of uterine contractility disorders. Keywords : Theobromacacao Cymbopogoncitratus , uterus, spontaneous contraction

Using PET imaging to track STING-induced interferon signaling

In the 19th century, Ilya Metchnikoff defined and broadened our initial understanding of phagocytosis and, in 1908, went on to show that a cellular component (i.e., DNA) stimulates immune responses (1). About a century later, Janeway conceptualized pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) (2). Since then, we know that PAMP recognition by innate immune cells via PRRs activates the production of several cytokines, including interferons (IFNs), with the eventual recruitment of lymphocytes. Subsequent research discovered that innate immune recognition of double-stranded DNA (dsDNA) triggers autoimmune diseases (3). However, before the discovery of dsDNA sensors, an endoplasmic reticulum (ER) protein encoded by the TMEM173 gene, known as a stimulator of IFN genes (STING), was identified as a significant factor involving DNA recognition in innate immunity (4). Subsequently, scientists discovered that the direct cytosolic DNA sensor (cGAS) activates the expression of type 1 IFNs (5). Today, it is well known that activation of cGAS-cGAMP-STING signaling is triggered by cytosolic DNA and is necessary for antimicrobial and antitumor immune responses. In PNAS, Liang et al. (6) describe an innovative process for monitoring STING-induced IFN signaling. Induction of IFN signaling by STING occurs on detection of cytoplasmic DNA, whichmay be tumor- or microbial-derived. STING is activated when cGAS catalyzes the synthesis of cyclic dinucleotides (CDNs) including 2′3′-cGAMP (7). STING is translocated from the ER to the perinucleus, phosphorylated by TANK-binding kinase 1 (TBK1) and recruits IFN regulatory factor 3 (IRF3), which in turn is phosphorylated by TBK1, forms a dimer, and enters the nucleus. Phosphorylated IRF3 activates transcription of type 1 IFNs and other relevant cytokines (8) which bind to the heterodimeric IFN receptors (IFNAR1 and IFNAR2) and recruits Janus family kinase 1(Jak1) and tyrosine kinase 2 (Tyk2), which in turn phosphorylates and activates IFNAR1 and IFNAR2. Activated IFNAR1 and 2 phosphorylate signal transducers and activators of transcription (STAT) proteins (STAT1 and STAT2), which are transferred to the nucleus along with IFN regulatory factor 9 (IRF9), to enhance transcription of IFN target genes (9) and subsequently activate the innate and adaptive immune responses

Ex vivo Inhibitory Activity of the Ethanol Root Extract of Senna occidentalis (Labaceae) on Isolated Rat Uterus

The ex vivo activity of the ethanol root extract of Senna occidentalis (Labaceae) on isolated rat uterus was examined in order to determine its potential in the therapy of uterine related pathologies. The ethanol root extract of S. occidentalis was investigated on the isolated uterus of rats primed with diethyl stilboestrol (0.1 mg/kg) 24 h prior to the experiment. The extract (2.5 and 7.5 mg/mL) effect on ACh (0.1 – 1.0 μg/mL)– induced contractility, in the presence of atropine (0.12 μg/mL), propranolol (8 μg/mL), CaCl2 (in Ca2+-free medium) and in the presence of 100 mM KCl was examined. The extract significantly inhibited ACh-induced uterine contractions (P< 0.05) and CaCl2- induced uterine contractions (in Ca2+-free medium) (P<0.05) in a non-competitive but concentration-dependent manner. A rightward shift of the concentration-response curve was observed in all cases. However, a bell- shaped concentration-response curve was observed for CaCl2. The inhibitory effect of the extract on ACh-induced uterine contractions was unaffected by propranolol. The extract (0.1 - 0.4 mg/mL) also inhibited KCl- induced uterine contractions. The root extract of S. Occidentalis was shown to inhibit agonist-induced uterine contractions probably through interaction with voltage-operated calcium channels. Keywords: Acetylcholine; Calcium; Propranolol; Ex vivo uterine activity; Senna occidentalis; Uteru

In vitro inhibitory effect of methanol leaf extract of Stachytarpheta jamaicensis (Verbenaceae) on nonpregnant rat uterus

Purpose: To investigate the effect of the methanol extract of the plant, Stachytarpheta jamaicensis (Verbenaceae) (SJ) on uterine smooth muscles of non-pregnant female rats, with the aim of examining the oxytocic or otherwise effect of the extract.Methods: In the first phase of experiments, the effects of SJ (0.41 and 4.01 mg/ml) on oxytocin (OT) induced uterine contractions were determined and repeated after addition of salbutamol (SBL) (41.7 nM). In the second phase, verapamil (VER) (2.03 μM), SBL (41.7 nM), and SJ (0.41 and 4.01 mg/ml) were applied to the tissues after pre-contraction with K+ (80 mM). In the third phase, the effects of VER, SBL, and SJ on CaCl2-induced contractions (0.03 – 10.83 mM) were examined. In the fourth and final phases, the second phase experiments were repeated in a calcium-free medium and in the absence and presence of propranolol (1.54 mM) respectively.Results: SJ exhibited significant inhibitory effects on OT and CaCl2 induced uterine contractions (p < 0.05). The EC50 for OT increased from 1.92 ± 0.12 to 7.16 ± 0.16 nM and that for CaCl2 increased from 0.19 ± 0.09 to 0.76 ± 0.11 mM in the presence of the extract. SJ also significantly inhibited KCl- induced contraction by 39.15 ± 2.13 and 53.23 ± 1.58 % for 0.41 and 4.01 mg/ml of the extract, respectively (p < 0.01); this inhibition was unaffected by propranolol. On the other hand, SBL and VER showed inhibition of 77.25 ± 1.85 and 79.44 ± 2.27 %, respectively.Conclusion: SJ exerts uterine inhibitory effects in rats which appear unrelated to β2-adrenergic receptor stimulation but possibly through inhibition of calcium entry into the cytoplasm.Keywords: Oxytocin, Calcium-free, Uterine contraction, β2-Adrenergic receptor stimulation, verapamil, salbutamol, Propranolol, S. jamaicensi

Prevalence of Pin Tract Infection: The Role of Combined Silver Sulphadiazine and Chlorhexidine Dressing

Infection at the pin tract is a common complication of external fixation. This study was done to compare the rate of pin site infection following combined 1 % silver sulphadiazine and 5 % chlorhexidine dressing with 5%chlorhexidine dressing alone. This was a prospective controlled study which compared the results of pin site dressing using a combination of chlorhexidine and silver sulphadiazine cream(Study group)with dressing using chlorhexidine alone. Eligible patients had external fixation in the treatment of open fractures or orthopaedic conditions. Pintract infectionwas deemed to be present if erythema, cellulitis or purulent discharge occurred around a pin site. We did not distinguish between deep and superficial infection. The study group had one hundred and seventy pin sites while the control group had one hundred and sixty-four pin sites. Thirty-eight patients, in whom thirty-seven uniplanar external fixators and one Ilizarov ring fixator were used, made up both groups. Three patients (7.9%) had pin tract infection in the study group while nine patients (23.7%) had pin tract infection in the control group. Therewas a significantly lower prevalence of pin-tract infection amongst patientswhose external fixation pins were dressed with 1 % silver sulphadiazine and 5 % chlorhexidine than in those dressed with chlorhexidine alone (P=0.03). Therefore, we advocate the use of a combination of silver sulphadiazine and chlorhexidine for pin site dressing.Keywords: External fixation, Prevalence, Pin-tract Infection,Dressings

Metabolomics-coupled functional pharmacology of chlorophyll compounds isolated from the leaves of Ficus Exasperata Vahl (Moraceae) provides novel pathways on myometrial activity

New chlorophyll derivatives (pheophytins along with pheophorbide derivatives) were isolated from the leaves of Ficus exasperata and were found to have varying effects on uterine contractility. The current study was therefore aimed at the utilization of mass spectrometry and nuclear magnetic resonance spectroscopy coupled with isolated uterine tissue assay as a platform to assist in the determination of the mechanism of activity of the isolated chlorophyll compounds from the plant F exasperata. The pheophytin and pheophorbide compounds (200 µg/mL) were added to the isolated uterine tissues. Mice uteri, treated with the pheophytin compounds, and the physiological buffer in which the uterine tissues were immersed, were rapidly collected and analyzed using high-resolution Fourier transform mass spectrometry and proton (1H) nuclear magnetic resonance for bioinformatics study. Resulting data were analyzed via pairwise chemometric comparison models, with P < .05 considered statistically significant. Primary signaling pathways found to be correlated with the pheophytins in this study included cyclic adenosine monophosphate, dopamine, extracellular signal-regulated kinases 1/2, and glutamate pathways

Open Inter Locked Nailing Without Targeting Device or X-Ray Guide in Revision Surgery for Non-Union of the Femur: A Case Report

We present a patient with non-union of the femur and fracture of the nail after Kuntscher nailing who went on to have union after interlocked nailing with a modified Kuntscher nail (K-nail). The interlocked intramedullary nailing was done without X-ray guide or targeting device. The essence of this report is to highlight the possibilities inherent in modification of devices and established procedures. The early result calls for a closer look at this cheap, safe and effective means of handling femoral non-union in third world societies where instrumentation and implants for interlocked nailing may not be readily available. Key Words: Interlocked-Intramedullary nail, Femur, Cortical window

Toward understanding myometrial regulation : metabolomic investigation reveals new pathways of oxytocin and ritodrine activity on the myometrium

In recent times, additional pathways involved in the regulation of the myometrium have been suggested. This also holds true for the effect of drugs such as oxytocin (OT) and β-adrenergic agonists on the myometrium. Knowledge of these additional pathways will certainly prove useful in designing better therapies for pathologies of the myometrium. This study was therefore aimed at investigating the possibility of other pathways involved in the activities of both OT and ritodrine (RIT; a β-adrenergic agonist) in the myometrium by utilizing metabolomics and bioinformatics. High-resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy coupled with functional uterine assays were used for an innovative assessment. In vitro pharmacological assay of OT (1 nmol/L) and RIT (0.1 nmol/L) on isolated mice uteri mounted in 3 mL organ baths was performed. Mice uteri, treated with OT or RIT, as well as the physiological buffer in which the uterine tissues were immersed, were rapidly collected and analyzed using HRFTMS, proton ((1)H)-NMR, and bioinformatics. Resulting data were analyzed via pairwise chemometric comparison models, with P ≤ .05 considered statistically significant. In addition to previously known metabolites, nicotinamide adenine dinucleotide, γ-aminobutyric acid, and sphingosine were significantly associated with the activity of OT, whereas the activity of RIT was associated with a downstream involvement of prostaglandin F1 and phosphatidylinositol signaling. These findings add evidence to the reports on additional regulation of myometrial activity by these drugs and suggest newer pathways for therapeutic manipulation

Open interlocked nailing without a targeting device or X-ray guidance for non-union of the femur: a case series

From October 2005 to August 2007, we operated on six patients who had femoral non-unions and performed interlocked intramedullary nailing without X-ray guidance or a targeting device. There were three fractures of the distal femur, two fractures of the mid-shaft and one of the proximal femur. Fatigue failure of a non-interlocked Kuntscher nail and one nail migration were the presenting features in two patients. The presence of sclerosis of the bone ends in four cases and a need for cancellous bone grafts at the site of non-union in all patients made wide dissection and open reduction unavoidable. There was a limb length discrepancy in all patients before surgical intervention. Partial weight bearing was commenced at 6 weeks post-operation. There was no case of wound infection. There was no misplaced screw. Minimum range of knee flexion was 105° at 2 months post-operation. These early results call for a closer look at this cheap, safe and effective means of handling femoral non-union in third world societies where there is paucity of instrumentation and implants for interlocked nailing