Incision Model Research Articles

Effects of magnesium sulfate administration in attenuating chronic postsurgical pain in rats

Chronic postsurgical pain (CPSP) is a serious issue for many postoperative patients. Though there are numerous treatment options for the prevention of CPSP, none of them is optimal as the mechanisms of the transition from acute to chronic postoperative pain have not been elucidated. Ketamine and opioids have been administered for chronic postoperative pain treatment but induce severe adverse reactions and/or physical dependency.Here, we examined whether pre-administration of the nonselective N-methyl-d-aspartate (NMDA) receptor antagonist magnesium sulfate attenuates CPSP behavior and alters the expression of glutamate ionotropic receptor NMDA type subunit 1a (Grin1 mRNA) in a rat skin/muscle incision and retraction (SMIR) model. We assessed the effects of a single subcutaneous magnesium sulfate injection on nociceptive behaviors including guarding pain, mechanical hyperalgesia, and heat hypersensitivity in rats after SMIR surgery. We used reverse transcription-quantitative PCR (RT-qPCR) to evaluate Grin1 mRNA expression in the dorsal horn of the spinal cord on postoperative day 14. Compared with the vehicle, magnesium sulfate administration before SMIR surgery reduced mechanical hyperalgesia for 17 d Grin1 gene expression was significantly higher on the ipsilateral side than the contralateral side (P = 0.001) on postoperative day 14. The magnesium sulfate injection prevented Grin1 mRNA upregulation in the spinal cord dorsal horn. A single magnesium sulfate injection mitigated SMIR-induced mechanical hyperalgesia possibly by modulating Grin1 expression. Preoperative magnesium sulfate administration could prove to be a simple and safe CPSP treatment.

Temporal profiling of uplift rate along an active fault using river long profile in the Kuchchh region, Western India

River long profiles are widely used as tectonic event markers. Incision/uplift rate estimations based on the dating of river terrace or exposed scarp sediment give long-term averaged uplift rate values with the limitation of not giving the intermediate phases of highs and lows. On the other hand, GPS based estimates provide only decadal-scale uplift rate estimates. In our study, we adopted the long profile inversion methodology to obtain a temporal profile of uplift rate history (over the Late Pleistocene-Holocene time period) along an active fault (the Kuchchh Mainland Fault) in Kuchchh region, western India, which has experienced several large magnitude earthquakes in recent past. We also used long profiles analysis to quantify the transient response of Kuchchh landscape to uplift activity along the Kuchchh Mainland Fault. Steepness index and chi profiles were estimated to display the spatial variability in landscape disequilibrium. Integral method-based chi profiles were used to obtain the optimum value of basin area exponent of the Stream Power Incision Model (SPIM). Our estimates provide a mean uplift rate value of 1.1–1.4 mm/yr along the Kuchchh Mainland Fault during the Late Pleistocene-Holocene period, which matches with the average uplift rate derived from other independent observations in this region. Further, a chronology of major tectonic phases from the estimated uplift rate time series also corroborates with field-based estimates of major incision events in Kuchchh region. We also tested the robustness and sensitivity of our uplift rate estimates to model parameters. Such data can be complementary to the existing sparsely (both spatially and temporally) distributed uplift rate database, which is imperative to seismic hazard assessment.

Effects and Characterization of Some Topical Ointments Based on Vegetal Extracts on Incision, Excision, and Thermal Wound Models.

The present paper aims to formulate and characterize four phytotherapeutic ointments based on Hippophae fructus, Calendulae flos, Bardanae folium, and Millefolii herba, which are included in a novel ointment base. In order to investigate the healing properties of the ointments, in vivo experimental wound models of linear incision, circular excision, and thermal burn were performed on Wistar rats. Topical treatment was performed daily for 21 days. Determination of the wound contraction rate (WCR), the period of reepithelization, and histopathological examination were achieved. Additionally, for the tested ointments, oscillatory and rotational rheological tests were carried out, and for the extracts, HPLC analysis was performed. The results demonstrate that the tested novel ointments are safe for use and the most effective ointment proved to be the one based on Arctium lappa, followed by that of Calendulae flos.

In vitro Antioxidant and in vivo Wound Healing Activities of the 80% Methanol Extract and Solvent Fractions of Seeds of Brassica carinata A. Braun (Brassicaceae) in Mice.

BackgroundBrassica carinata is one of the traditional medicinal plants used in Ethiopia for the treatment of wounds and other diseases. However, the plant has not been scientifically validated, and thus the present study evaluated the in vitro anti-oxidant and the in vivo wound healing activity of the crude extract and solvent fractions of B. carinata seeds in mice.Materials and MethodsThe crude extract was prepared by maceration using 80% methanol and formulated as 5% and 10% w/w ointments for topical application. The acute dermal toxicity was performed in female albino rats based on Organization for Economic Cooperation and Development (OECD) guideline number 434. Excision and incision wound healing models were used to evaluate the wound healing activities of crude extract and solvent fractions ointments in mice. Wound healing parameters such as wound area contraction and the period of epithelialization were determined in an excision model, whereas tensile strength was determined in an incision model. Moreover, the crude extract and solvent fractions were evaluated for the free radical scavenging activities in DPPH assay.ResultsThe acute dermal toxicity test showed that a limit dose of 2,000 mg/kg of 10% w/w crude extract ointment did not cause dermal toxicity in mice. In the excision wound model, the data revealed that 10% w/w ointment exhibited a significant wound contraction (from day 6 to 16, P<0.001) effect with a significant decrease in epithelization period (at day 14, P<0.001). In addition, 5% ointment of the crude extract showed a significant effect in wound contraction (from day 8 onwards, P<0.01) and epithelization period (at day 16, P<0.01). Despite all fractions being shown to promote wound healing, 10% w/w aqueous and ethyl acetate fractions showed a significant wound contraction (P<0.001) effect starting from the 4th day onwards. Besides, the maximum antioxidant activity was seen in the aqueous fraction with an IC50 value of 3.45±0.12 mg/mL.ConclusionThe present study demonstrated that the 80% methanol extract and solvent fractions of the seeds of B.carinata possess potential wound healing and anti-oxidant effects, supporting the traditional use of the plant for wound management.

Acid-sensing Ion Channel 3 Overexpression in Incisions Regulated by Nerve Growth Factor Participates in Postoperative Nociception in Rats.

Acid-sensing ion channel 3 (ASIC3) upregulation has been reported in dorsal root ganglion neurons after incision and contributes to postoperative nociception. This study hypothesized that upregulation of ASIC3 in incised tissues is induced by nerve growth factor through the phosphoinositide 3-kinase/protein kinase B signaling pathway. A plantar incision model was established in adult male and female Sprague-Dawley rats. ASIC3 was inhibited by APETx2 treatment, small interfering RNA treatment, or ASIC3 knockout. Sciatic nerve ligation was performed to analyze ASIC3 transport. A nerve growth factor antibody and a phosphoinositide 3-kinase inhibitor were used to investigate the mechanism by which nerve growth factor regulates ASIC3 expression. Acid-sensing ion channel 3 inhibition decreased incisional guarding and mechanical nociception. ASIC3 protein levels were increased in skin and muscle 4 h after incision (mean ± SD: 5.4 ± 3.2-fold in skin, n = 6, P = 0.001; 4.3 ± 2.2-fold in muscle, n = 6, P = 0.001). Sciatic nerve ligation revealed bidirectional ASIC3 transport. Nerve growth factor antibody treatment inhibited the expression of ASIC3 (mean ± SD: antibody 2.3 ± 0.8-fold vs. vehicle 4.9 ± 2.4-fold, n = 6, P = 0.036) and phosphorylated protein kinase B (mean ± SD: antibody 0.8 ± 0.3-fold vs. vehicle 1.8 ± 0.8-fold, n = 6, P = 0.010) in incised tissues. Intraplantar injection of nerve growth factor increased the expression of ASIC3 and phosphorylated protein kinase B. ASIC3 expression and incisional pain-related behaviors were inhibited by pretreatment with the phosphoinositide 3-kinase inhibitor LY294002. Acid-sensing ion channel 3 overexpression in incisions contributes to postoperative guarding and mechanical nociception. Bidirectional transport of ASIC3 between incised tissues and dorsal root ganglion neurons occurs through the sciatic nerve. Nerve growth factor regulates ASIC3 expression after plantar incision through the phosphoinositide 3-kinase/protein kinase B signaling pathway.

Effects of nicorandil on p120 expression in the spinal cord and dorsal root ganglion of rats with chronic postsurgical pain.

Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanism is not well understood. Accumulating evidence has suggested that central sensitization is the main mechanism of pain. To study the role of p120 in CPSP, a skin/muscle incision and retraction (SMIR) model was established, and immunofluorescence staining and western blotting were performed to analyze the expression of p120 in the spinal cord and dorsal root ganglion (DRG). The results demonstrated that SMIR increased the expression of p120 in the DRG and the spinal cord compared with the naive group. Furthermore, it was demonstrated that p120 was mainly distributed in the glial fibrillary acidic protein-positive astrocytes in the spinal cord, and in the neurofilament 200-positive medium and large neurons in the DRG. Our previous studies have shown that adenosine triphosphate-sensitive potassium channel (KATP) agonists can reduce postoperative pain in rats. Therefore, the changes in p120 were observed in the DRG and spinal cord of rats following the intraperitoneal injection of nicorandil, a KATP agonist. It was demonstrated that nicorandil administration could relieve mechanical pain experienced following SMIR in rats, and decrease the expression of p120 in the DRG and spinal cord. The results revealed that p120 may contribute to the prophylactic analgesic effect of nicorandil, thus providing a novel insight into the mechanism of CPSP prevention.

Comparison of the efficacy of five standard topical hemostats: a study in porcine liver and spleen models of surgical bleeding

BackgroundSeveral topical hemostats are available to help control surgical bleeding. Cutanplast is a highly absorbent and porous gelatin product that is available in Fast sponge and powder forms. This study investigated the hemostatic efficacy of Cutanplast Standard and Fast gelatin sponge and powder and Emosist oxidized regenerated cellulose (ORC) gauze in porcine liver and spleen surgical bleeding models.MethodsCutanplast Standard and Fast gelatin sponge and Emosist ORC gauze were tested in liver abrasion/incision, liver puncture and spleen incision/puncture injuries, and Cutanplast Standard and Fast gelatin powder products were tested in liver abrasion/incision injuries. There were 13 liver injury (five abrasion, five incision and three puncture) and six spleen injury (three puncture and three incision sites) sites per animal.ResultsRapid hemostasis (≤ 2–5 min) was achieved in the liver abrasion and incision models with all Cutanplast gelatin sponge and powder products and Emosist ORC gauze, except in the liver incision model, time to hemostasis was > 5 min with Cutanplast Standard gelatin powder and Emosist ORC gauze. Rapid hemostasis occurred with Cutanplast Fast gelatin sponge and Emosist ORC gauze in the liver puncture and spleen puncture and incision models. In the spleen incision model, Cutanplast Standard gelatin sponge had a time to hemostasis approaching 10 min.ConclusionCutanplast gelatin sponge and powder products and Emosist ORC gauze may be suitable for surgical applications involving parenchymal organ bleeding, but certain products may perform better than others, including Cutanplast gelatin powder in diffuse mild bleeding (such as liver abrasion), and Cutanplast Fast gelatin sponge and Emosist ORC gauze for splenic bleeding.

Wound Healing Activities of Latex of Grassleaf Spurge (&lt;i&gt;Euphobia &lt;/i&gt;&lt;i&gt;g&lt;/i&gt;&lt;i&gt;raminea&lt;/i&gt;&lt;i&gt; &lt;/i&gt;Jacq.)

The present study evaluated the wound healing potentials of E. graminea (EG) latex. The latex of EG was screened for the presence of phytochemical constituents; in vitro antioxidant property and erythrocyte membrane stabilizing activity was used to investigate anti-inflammatory property of the latex. The wound healing potential of E. graminea latex (EGL) was investigated via incision and dead space wound models in wistar rats; eighteen wistar rats (separately for each model) were randomly divided into 3 groups (6 in each group): Group A: wound + EGL ; Group B: wound + Gentamycin (G); Group C: wound without treatment (control). Wound breaking strength (Incision model), hexuronic acid and hexosamine concentrations, activities of antioxidants biomolecules (superoxide dismutase, catalase, and reduced glutathione) as well as the levels of free radicals (nitric oxide-NO, malondialdehyde -MDA) were evaluated in the granulation tissue (dead space model) of experimental rats. The result of the study revealed that EGL tested positive for the presence of saponins, alkaloids, triterpenes, flavonoids and cardiac glycosides. Also, EGL contained an appreciable concentration of total flavonoids and phenolics. The latex exhibited mild ferric reducing power, inhibited DPPH in dose dependent manner as well as protected red blood cells against hypotonic and heat induced lyses. In wound incision model, EGL exhibited 13.6 % increase in wound breaking strength when compared to the control animals. Also, in dead space wound model, there was significant increase (p < 0.05) in hexoxamine, hexuronic acid and GSH concentrations as well as SOD activity in EGL and gentamycin treated wound compared to the control. Furthermore, there was a significant reduction (p < 0.05) in MDA concentration in EGL and gentamycin treated wound compared to the control while NO level and catalase activity showed no significant difference. This study revealed that EGL contained potentially bioactive molecules that could be employed in the treatment of wound.

EVALUATION OF EXCISIONAL AND INCISIONAL WOUND HEALING ACTIVITY OF ELECTROHOMEOPATHIC DRUG (SPAGYRIC ESSENCE) GREEN ELECTRICITY IN RATS

Objective: The current research is an attempt to evaluate the wound healing activity of Electrohomeopathic drug Green electricity (GE) in Wistar rats. No data have been reported till date on the wound healing effect of GE. Hence the present research focuses on the scientific investigation of the wound healing activity of GE in rats.&#x0D; Methods: Excision and incision wounds were inflicted upon albino rats. In the excision wound model, the wound contraction, Scar residue, area and time of complete epithelization were measured subsequently on day 0, 3,6,9,12,15, 18 and 21 after inflicting the wound. Wound contraction was calculated as a percentage change in the initial wound size. In the incision wound model, the tensile strength was measured on the 10th post wounding day.&#x0D; Results: It was noted that the effect produced by the GE Showed significant wound healing (p&lt;0.01) in all wound models when compared to the control group. In the case of the excision model, GE statistically increases the wound contraction rate and in the case of the incision model GE showed high tensile strength as compared to the control group. In both cases the epithelization period was significantly decreased as compared to control. Almost 100% wound protection was achieved by GE in 21 d as compared to control.&#x0D; Conclusion: GE (ointment) showed significant wound healing activity (p&lt;0.01) in both the excised wound model and incision wound model in rats.

Antioxidant, Antimicrobial and Wound Healing Potential of Helicteres isora Linn. Leaf Extracts

ObjectiveTo investigate the antioxidant, antimicrobial and wound healing potential of Helicteres isora Linn. leaf extracts. MethodsThe petroleum ether, chloroform, acetone, ethanol and hydroalcoholic extracts of leaves were screened for phytochemicals. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging tests and reducing power assays were performed to measure antioxidant activity; disc diffusion methods were used to evaluate antimicrobial potential. Wound healing activity was evaluated by incision and excision wound rat models. ResultsThe extracts contained mainly sterols and flavonoids. The hydroalcoholic extract showed remarkable antioxidant and antimicrobial potential and significant (P < 0.05) wound healing activity. ConclusionsThe identified activities of the hydroalcoholic extract may be attributable to its constituent phytochemicals.

Calibrating fluvial erosion laws and quantifying river response to faulting in Sardinia, Italy

It is now widely accepted that rivers modify their erosion rates in response to variable rock uplift rates, resulting in changes in channel slope that propagate upstream through time. Therefore, present-day river morphology may contain a record of tectonic history. The simple stream power incision model can, in principle, be used to quantify past uplift rates over a variety of spatial and temporal scales. Nonetheless, the erosional model's exponents of area and slope (m and n respectively) and ‘bedrock erodibility’ (k) remain poorly constrained. In this paper, we will use a geologically and geomorphically well constrained Plio-Pleistocene volcanic landscape in central Sardinia, Italy, to calibrate the stream power erosion equation and to investigate the slip rate of faults that have been seismically quiescent in the historic past. By analysing digital elevation models, geological maps and Landsat imagery, we have identified the geomorphic expression of several volcanic features (eruption centres and basaltic lava flows) and three normal faults with 6 to 8 km fault traces within the outcrop. Downstream, river longitudinal profiles show a similar transient response to relative base level fall, probably as a result of relief inversion at the edge of the volcanic outcrop. From measurements of incision, local slope and upstream catchment area across eight different rivers, we calculate n ≈ 1, m = 0.50 ± 0.02 and, using a landscape age from literature of 2.7 Ma, bedrock erodibility k = 0.10 ± 0.04 m(1−2m) Myr−1. There are also knickpoints on rivers upstream of two normal faults, and we used numerical inverse modelling of the longitudinal profiles to predict the slip rate of these faults since 2.7 Ma. The results from the inverse model show that the erosional parameter values derived in this study can produce theoretical longitudinal profiles that closely resemble observed river profiles upstream of the faults. The lowest misfit theoretical longitudinal profiles were generated by a model of temporally discontinuous footwall uplift with consistently low throw rates (<0.1 mm yr−1). The predicted footwall uplift history is similar for the two faults, both showing periods of fault slip and no fault movement since 2.7 Ma.

GIS and DEM based analysis of incision and drainage reorganization of the Buyuan River basin in the upper Lancang-Mekong of China since the Late Pleistocene

River incision and drainage reorganization have an important impact on the site selection of many major projects including city, road and others, and are the key issues of Quaternary environmental changes. Studies of river incision and river-network adjustment have traditionally been based on extensive field evidence, such as sediment age and beheaded river system. The Buyuan River basin is a large sub-basin of the upper Lancang-Mekong, with high mountains and extremely active erosion. The latter affects the preservation of the Quaternary period sediments leading to difficulties in understanding the main evolution characteristics of the basin. This study investigates differences in the equilibrium state of the longitudinal profile, infers incision rates, and evaluates drainage divide migration timelines using the stream-power incision model, the latest morphological dating, and Chi-plots (χ-z) based on digital elevation models (DEMs) on the GIS software platform. The final results show that two significant erosion base-level decreases occurred in the Late Pleistocene at least. The incision rate of the mainstream might have been 0–2.99 mm/yr since 100 ka BP and 0–3.28 mm/yr since 46 ka BP. The Chi-values across the divides suggest that space limited (or constrained) river reorganization and that there is no severe reorganization in the basin; the imbalance of traceable erosion only exists in local areas. The main driving force for the geomorphologic evolution of the Buyuan River basin is likely climate fluctuations rather than strong tectonic uplift since the Late Pleistocene.

In vivo bioactivity assessment on Epilobium species: A particular focus on Epilobium angustifolium and its components on enzymes connected with the healing process

Ethnopharmacological relevanceEpilobium species are generally known as “Yakı Otu” in Turkey, which mens “plaster herb” in English. Young shoots of Epilobium angustifolium L., Epilobium stevenii Boiss., and Epilobium hirsutum L. are consumed as salad or meal. These species have been used as a poultice for the treatment of mouth wounds in traditional medicine. An ointment prepared from leaves is used for skin disorders in children. Aim of the studyWe aimed to evaluate the ethnopharmacological use of Epilobium angustifolium, E. stevenii, and E. hirsutum by using in vivo and in vitro experimental models, and to identify the active wound-healer compound(s) and to explain the probable mechanism of the wound-healing activity. Materials and methodsEvaluation of wound healing effects of plant extracts was performed in rats and mice by linear incision and circular excision wound models. Determination of total phenolic constituents and antioxidant capacities, which are known to promote the wound healing process, were carried out through Folin-Ciocalteau method and 2,2 Diphenyl 1 picrylhydrazyl (DPPH) scavenging assay as well as determination of total antioxidant status (TAS) and total oxidant status (TOS) on the treated tissues. The active ethyl acetate (EtOAc) sub-extract of E. angustifolium was fractionated by different chromatographic separation techniques. The structures of isolated compounds were elucidated via detailed analyzes (NMR and LC/MS). In addition, in vitro collagenase, hyaluronidase, and elastase enzymes inhibitory activity tests were performed on the isolated compounds to discover the activation pathways of the samples. ResultsAmong the methanol (MeOH) extracts, E. angustifolium had the highest wound healing activity. Among the sub-extracts, EtOAc showed the highest wound healing activity. Thus, EtOAc sub-extract was subjected to chromatography to isolate the active compounds. Five known flavonoids namely hyperoside (quercetin-3-O-β-D-galactoside) (1), kaempferol (2), kaempferol-3-O-α-L-rhamno pyranoside (3), quercetin-3-O-α-L-rhamno pyranoside (4), and quercetin-3-O-α-L-arabino pyranoside (5) were isolated from the EtOAc sub-extract of E. angustifolium. In vitro tests showed that hyperoside could be the compound responsible for the wound-healing activity by its significant anti-hyaluronidase, anti-collagenase, and antioxidant activities. ConclusionThe EtOAc sub-extract of the aerial part of Epilobium angustifolium displayed remarkable wound-healing activity with anti-hyaluronidase, anti-collagenase, and antioxidant activities. Hyperoside was detected as the primary active compound of the aerial parts. According to the results, we suggest that EtOAc sub-extract of E. angustifolium and hyperoside may be a potent nominee to be used for the improvement of a wound-healing agent.

Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain

BackgroundActivated astrocytes play important roles in chronic post-surgical pain (CPSP). Recent studies have shown reactive astrocytes are classified into A1 and A2 phenotypes, but their precise roles in CPSP remain unknown. In this study, we investigated the roles of spinal cord A1 and A2 astrocytes and related mechanisms in CPSP.MethodsWe used a skin/muscle incision and retraction (SMIR) model to establish a rat CPSP model. Microglia, CXCR7, and the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways were regulated by intrathecal injections of minocycline (a non-specific microglial inhibitor), AMD3100 (a CXCR7 agonist), and LY294002 (a specific PI3K inhibitor), respectively. Mechanical allodynia was detected with von Frey filaments. The changes in microglia, A1 astrocytes, A2 astrocytes, CXCR7, and PI3K/Akt signaling pathways were examined by enzyme-linked immunosorbent assay (ELISA), western blot, and immunofluorescence.ResultsMicroglia were found to be activated, with an increase in interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q) in the spinal cord at an early stage after SMIR. On day 14 after SMIR, spinal cord astrocytes were also activated; these were mainly of the A1 phenotype and less of the A2 phenotype. Intrathecal injection of minocycline relieved SMIR-induced mechanical allodynia and reverted the ratio of A1/A2 reactive astrocytes. The expression of CXCR7 and PI3K/Akt signaling was decreased after SMIR, while they were increased after treatment with minocycline. Furthermore, intrathecal injection of AMD3100 also relieved SMIR-induced mechanical allodynia, reverted the ratio of A1/A2 reactive astrocytes, and activated the PI3K/Akt signaling pathway, similar to the effects produced by minocycline. However, intrathecal injection of AMD3100 did not increase the analgesic effect of minocycline. Last, LY294002 inhibited the analgesic effect and A1/A2 transformation induced by minocycline and AMD3100 after SMIR.ConclusionOur results indicated that microglia induce the transformation of astrocytes to the A1 phenotype in the spinal cord via downregulation of the CXCR7/PI3K/Akt signaling pathway during CPSP. Reverting A1 reactive astrocytes to A2 may represent a new strategy for preventing CPSP.

Preparation of external herbal formulation for wound healing activity

Wound healing is a tedious process involving multiple parameters. Wounds happen during trauma, sports, skin burning etc. Skin is the largest organ in terms of surface area. Skin is composed of triple helical collagen tissue which is giving strength to skin. In this experiment attempt was made to determine the wound healing activity of selected medicinal plants mainly Acorus calamus, Hibiscus rosasinenesis, Mimosa pudica which are available in our locality. The plants were extracted with solvents selected from previous research activities. The preliminary phytochemical screening was performed to know the major phytochemical in each plant extract. The creams were prepared using oleaginous base, absorption base, preservative and flavouring agent as prescribed by official books. Accelerated Stability study of six months was performed on creams and best stable cream was used for further activity. Acute toxicity study was performed to know the therapeutic dose and toxic dose of extracts. Determined Wound healing activity using major two models excision wound model and incision model, which are used to identify percentage, wound closure and tensile strength of newly synthesized skin. Further the major marker amino acid compound Hydroxyproline was determined as a supporting factor to the wound healing activity. By this study we come to conclusion that the selected medicinal plants are good wound healing herbs if prescribed in correct dosage form and appropriate formulation suitable to the better skin compatibility.

Drainage conformation and transient response of river system in thrust segmentation of Northwest Himachal Himalaya, India

In the northwest Himalayan region, the ongoing out-of-sequence deformation caused emergence of Back Thrust (BT) around 43ka, which attributed the growth of anticlines parallel to the strike of major thrusts. This spatial and temporal geomorphic deformation is accompanied by coexisting river incision in the axial zone of anticlines and base-level fall along with upstream migration of knickpoints in the longitudinal river course. We used the Stream Power Incision model (SPIM) which relates the normalized steepness index (ksn), and concavity index (θref) with the slope (S) of longitudinal river profile as a power-law function of upstream area (A). and estimated these parameters for Beas, Soan, and Sutlej rivers to decipher the spatial distribution of deformation pattern. Using SRTM DEM and based on strike parallel variations of the ksn we identified segmented nature of the NW Himalayan thrusts. Further, the dynamics of river basins and transience along the tributaries and main stem rivers has been analyzed by Chi analysis (χ), which is attributed to geometric disequilibrium of the rivers. The results of ksn and χ analysis together suggests that the crustal shortening of NW Himalaya is caused by segmental reactivation of the thrusts. Further, investigating the change in steepness along longitudinal course aids in understanding the differential uplifts patterns in actively deforming segments of major NW Himalayan thrusts.

Peripheral tetrahydrobiopterin is involved in the pathogenesis of mechanical hypersensitivity in a rodent postsurgical pain model.

Because treatment for postsurgical pain (PSP) remains a major unmet medical need, the emergence of safe and innovative nonopioid drugs has been strongly coveted. Tetrahydrobiopterin (BH4) is an interesting molecule for gaining a better understanding the pathological mechanism of neuropathic pain. However, whether BH4 and its pathway are involved in the pathogenesis of PSP remains unclear. In this study, we found that early in a rat paw incision model, the gene expression of GTP cyclohydrolase 1 (GTPCH) and sepiapterin reductase (SPR), BH4-producing enzymes in the de novo pathway, were significantly increased in incised compared with naive paw skin. Although a significant increase in GTPCH protein levels was observed in incised paw skin until only 1 day after incision, a significant increase in BH4 levels was observed until 7 days after incision. In vivo, Spr-knockout mice showed an antinociceptive phenotype in the hind paw incision compared with the wild-type and Spr heterozygote groups. Furthermore, QM385, the SPR inhibitor, showed a significant dose-dependent, antinociceptive effect, which was supported by a reduction in BH4 levels in incised skin tissues, with no apparent adverse effects. Immunohistochemical analysis demonstrated that macrophages expressing GTPCH protein were increased around the injury site in the rat paw incision model. These results indicate that BH4 is involved in the pathogenesis of PSP, and that inhibition of the BH4 pathway could provide a new strategy for the treatment of acute PSP.

Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model

ABSTRACT Surgical site infection risk continues to increase due to lack of efficacy in current standard of care drugs. New methods to treat or prevent antibiotic-resistant bacterial infections are needed. Multivalent Adhesion Molecules (MAM) are bacterial adhesins required for virulence. We developed a bacterial adhesion inhibitor using recombinant MAM fragment bound to polymer scaffold, mimicking MAM7 display on the bacterial surface. Here, we test MAM7 inhibitor efficacy to prevent Gram-positive and Gram-negative infections. Using a rodent model of surgical infection, incision sites were infected with antibiotic-resistant bioluminescent strains of Staphylococcus aureus or Pseudomonas aeruginosa. Infections were treated with MAM7 inhibitor or control suspension. Bacterial abundance was quantified for nine days post infection. Inflammatory responses and histology were characterized using fixed tissue sections. MAM7 inhibitor treatment decreased burden of S. aureus and P. aeruginosa below detection threshold. Bacterial load of groups treated with control were significantly higher than MAM7 inhibitor-treated groups. Treatment with inhibitor reduced colonization of clinically-relevant pathogens in an in vivo model of surgical infection. Use of MAM7 inhibitor to block initial adhesion of bacteria to tissue in surgical incisions may reduce infection rates, presenting a strategy to mitigate overuse of antibiotics to prevent surgical site infections.

Parameterization of river incision models requires accounting for environmental heterogeneity: insights from the tropical Andes

Abstract. Landscape evolution models can be used to assess the impact of rainfall variability on bedrock river incision over millennial timescales. However, isolating the role of rainfall variability remains difficult in natural environments, in part because environmental controls on river incision such as lithological heterogeneity are poorly constrained. In this study, we explore spatial differences in the rate of bedrock river incision in the Ecuadorian Andes using three different stream power models. A pronounced rainfall gradient due to orographic precipitation and high lithological heterogeneity enable us to explore the relative roles of these controls. First, we use an area-based stream power model to scrutinize the role of lithological heterogeneity in river incision rates. We show that lithological heterogeneity is key to predicting the spatial patterns of incision rates. Accounting for lithological heterogeneity reveals a nonlinear relationship between river steepness, a proxy for river incision, and denudation rates derived from cosmogenic radionuclide (CRNs). Second, we explore this nonlinearity using runoff-based and stochastic-threshold stream power models, combined with a hydrological dataset, to calculate spatial and temporal runoff variability. Statistical modeling suggests that the nonlinear relationship between river steepness and denudation rates can be attributed to a spatial runoff gradient and incision thresholds. Our findings have two main implications for the overall interpretation of CRN-derived denudation rates and the use of river incision models: (i) applying sophisticated stream power models to explain denudation rates at the landscape scale is only relevant when accounting for the confounding role of environmental factors such as lithology, and (ii) spatial patterns in runoff due to orographic precipitation in combination with incision thresholds explain part of the nonlinearity between river steepness and CRN-derived denudation rates. Our methodology can be used as a framework to study the coupling between river incision, lithological heterogeneity and climate at regional to continental scales.

Wound healing activity of skin incision and skin burn from spray gel formula contains combination of banana stem (Musa acuminata Colla) and Aloe vera ethanol extracts on mice

Various studies reports the activity of wound healing from banana stem (Musa species) and also Aloe vera individually. This research purpose are to identify the wound healing activity of skin incision and skin burn animal model from spray gel formula contains combination of Musa paradisiaca Colla and Aloe vera L ethanol extracts on mice. This research were used randomized post test only control group design. Each of incision wound and burn wound models were used 28 mice and divided into 7 group. Group I was given with banana stem extract (BSE) 10%. Group II was given with Aloe vera extract (AVE) 10%. Group III was given with 7,5% BSE and 2,5% AVE. Group IV was given with 5% BSE and 5% AVE. Group V was given with 2,5% BSE and 7,5% AVE. Group VI and group VII (povidone iodine) as vehicle and positive control respectively. All group were sprayed twice a day from first day until seventh day after skin incision/burn induction, and length of wound/wound diameter were observed everyday. The result showed that combination of BSE and AVE had wound healing activity in both wound model which did not different significantly compared with individual extract.