Swarna Bhasma Induces Antigen-Presenting Abilities of Macrophages and Helps Antigen Experienced CD4+ T Cells to Acquire Th1 Phenotypes Against Leishmania donovani Antigens.

In leishmaniasis, the protective immunity is largely mediated by proinflammatory cytokine producing abilities of T cells and an efficient parasite killing by phagocytic cells. Notwithstanding a substantial progress that has been made during last decades, the mechanisms or factors involved in establishing protective immunity against Leishmania are not identified. In ancient Indian literature, metallic "bhasma," particularly that of "swarna" or gold (fine gold particles), is indicated as one of the most prominent metal-based therapeutic medicine, which is known to impart protective and curative properties in various health issues. In this work, we elucidated the potential of swarna bhasma (SB) on the effector properties of phagocytes and antigen-activated CD4+ T cells in augmenting the immunogenicity of L. donovani antigens. The characterization of SB revealing its shape, size, composition, and measurement of cytotoxicity established the physiochemical potential for its utilization as an immunomodulator. The activation of macrophages with SB enhanced their capacity to produce nitric oxide and proinflammatory cytokines, which eventually resulted in reduced uptake of parasites and their proliferation in infected cells. Further, in Leishmania-infected animals, SB administration reduced the generation of IL-10, an anti-inflammatory cytokine, and enhanced pro-inflammatory cytokine generation by antigen activated CD4+ T cells with increased frequency of double (IFNγ+/TNFα+) and triple (IFNγ+TNFα+IL-2+) positive cells and abrogated disease pathogeneses at the early days of infection. Our results also suggested that cow-ghee (A2) emulsified preparation of SB, either alone or with yashtimadhu, a known natural immune modulator which enhances the SB's potential in enhancing the immunogenicity of parasitic antigens. These findings suggested a definite potential of SB in enhancing the effector functions of phagocytes and CD4+ T cells against L. donovani antigens. Therefore, more studies are needed to elucidate the mechanistic details of SB and its potential in enhancing vaccine-induced immunity.

Bloqueo ecoguiado del nervio obturador al nivel de la rama púbica superior: estudio en cadáver embalsamado en Thiel utilizando látex / Sonographic obturator nerve block at level of superior pubic ramus: A Thiel based cadaveric investigation with latex

Introducción: El bloqueo del nervio obturador proximal tiene una eficacia similar al bloqueo del nervio obturador distal. Los estudios en cadáveres previos que inyectaban azul de metileno y realizaban seguidamente la disección reflejaron que la solución se dispersa a las divisiones anterior y posterior del nervio obturador, en el punto de salida del canal obturador. La absorción de azul de metileno por parte de la fascia y los músculos oscurece la delineación exacta de los nervios teñidos. Nosotros conjeturamos que la inyección de látex al nivel de las ramas púbicas superiores en el plano entre los músculos pectíneo y obturador externo mediante guía ecográfica a tiempo real, seguida de disección demorada en un cadáver embalsamado en Thiel, sería la técnica óptima de investigación en cadáveres. Métodos: Obtuvimos 3 cuerpos donados a la ciencia (BDTS) conforme a las normas estrictas del programa de donación del Departamento de Anatomía Macroscópica y Clínica de la Universidad de Medicina de Graz, y a la normativa sobre enterramientos de Estiria. Los BDTS fueron embalsamados utilizando el método de Thiel, que aporta condiciones muy realistas para las investigaciones con anestesia regional. En 2 cadáveres, las inyecciones de látex se realizaron de forma ecoguiada, y en el tercero se realizaron secciones transversales. Resultados: Nuestras disecciones abiertas de los cadáveres embalsamados en Thiel (C1 y C2) reflejaron que la inyección única de látex en el plano interfascial entre los músculos pectíneo y obturador externo al nivel de la rama púbica superior originó una dispersión adecuada a lo largo del tronco del nervio obturador y sus ramas, en todas las muestras. Conclusiones: La inyección ecoguiada de látex dentro del plano al nivel de las ramas púbicas superiores entre los músculos pectíneo y obturador externo cubre las ramas anterior y posterior y el tronco del nervio obturador.(AU)

Introduction: A proximal obturator nerve block has a similar block efficacy as the distal obturator nerve block. Previous cadaveric investigation injecting methylene blue dye solution and an immediate dissection proved the solution engulfing the anterior and posterior divisions of the obturator nerve as they emerge from the obturator canal. Uptake of methylene blue dye by the fascia and muscles obscures the exact delineation of the stained nerves. We hypothesized that injection of latex at the level of superior pubic rami in the plane between pectineus and obturator externus under real time ultrasound and a delayed dissection in a Thiel-based cadaver would be the optimal cadaveric investigational technique. Methods: Three investigated bodies donated to science (BDTS) fall under the strict rules of the donation program of the Department of Macroscopic and Clinical Anatomy of the Medical University of Graz and the Styrian burial law. The BDTS were embalmed with Thieĺs method which provides very lifelike conditions for investigations with regional anaesthesia backgrounds. In two cadavers (a total of specimens), latex injections were performed under ultrasound, while in the third cadaver cross-sections were executed. Results: Our Thiel based cadaveric open dissection (C1 and C2) demonstrated that a single injection of latex in the inter-fascial plane between the pectineus muscle and the obturator externus muscle at the level of superior pubic ramus led to adequate spread along trunk of the obturator nerve and its branches in all specimens. Conclusions: An in-plane ultrasound-guided latex injections at the level of superior pubic rami, between the pectineus and the obturator externus muscles soaks the anterior ramus, posterior ramus, and the obturator nerve trunk.(AU)

Evaluation of the cytotoxicity, oral toxicity, genotoxicity, and mutagenicity of the latex extracted from Himatanthus drasticus (Mart.) Plumel (Apocynaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Himatanthus drasticus is a tree popularly known as janaguba. Endemic to Brazil, it is found in the Cerrado and Caatinga biomes, rock fields, and rainforests. Janaguba latex has been used in folk medicine for its antineoplastic, anti-inflammatory, analgesic, and antiallergic activities. However, studies investigating the safety of its use for medicinal purposes are limited. AIM OF THE STUDY: This study aimed to evaluate the toxicity of the latex extracted from H. drasticus. MATERIALS AND METHODS: The latex was extracted from H. drasticus specimens by removing a small area of bark (5 × 30 cm) and then dissolving the exudate in water and lyophilizing it. Phytochemical screening was performed by TLC and GC-MS, protein, and carbohydrate levels. Cell viability was performed by the MTT method. Acute oral toxicity, genotoxicity, and mutagenicity assays were performed in mice. RESULTS: TLC showed the presence of saponins and reducing sugars, as well as steroids and terpenes. The GC-MS analysis of the nonpolar fraction identified lupeol acetate, betulin, and α/ß-amyrin derivatives as the major compounds. The latex was toxic to S-180 cells at 50 and 100 µg/mL. No signals of toxicity or mutagenicity was found in mice treated with 2000 mg/kg of the latex, but genotoxicity was observed in the Comet assay. CONCLUSIONS: H. drasticus latex showed toxicity signals at high doses (2000 mg/kg). Although the latex was not mutagenic to mice, it was genotoxic in the Comet assay in our experimental conditions. Even testing a limit dose of 2000 mg/kg, which is between 10 to 35-fold the amount used in folk medicine, caution must be taken since there is no safe level for genotoxic compounds exposure. Further studies on the toxicological aspects of H. drasticus latex are necessary to elucidate its possible mechanisms of genotoxicity.

Eosinophilic esophagitis during latex desensitization

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Larvicidal effect of the leaf latex of Aloe yavellana Reynolds and its major compounds against Amblyomma variegatum (Ixodidae).

The leaf latex of Aloe yavellana Reynolds is traditionally used for the treatment of various illnesses of humans and domestic animals in Ethiopia. In the present study, the latex and two major compounds isolated from it, namely, aloin A/B and microdontin A/B were assessed for their larvicidal activity against Amblyomma variegatum tick larvae using a larval packet test (LPT). The LC50 and LC99 of the latex were found to be 35.82 ± 2.27 and 83.48 ± 3.95 mg/ml, respectively. Although microdontin A/B showed better larvicidal activity (LC50 = 89.40 ± 4.45 mg/ml) than aloin A/B (LC50 = 257.69 ± 6.31 mg/ml), neither of the isolated compounds was as active as the latex suggesting that the compounds acted synergistically or minor compounds with potent larvicidal activity may exist in the latex. The results confirmed that the leaf latex of A. yavellana and its isolated compounds could have the potential to be used as larvicidal against A. variegatum ticks.

Double impact: natural molluscicide for schistosomiasis vector control also impedes development of Schistosoma mansoni cercariae into adult parasites.

BACKGROUND: Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite's biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite's life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts. METHODOLOGY/PRINCIPAL FINDINGS: We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics. CONCLUSIONS/SIGNIFICANCE: We describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).

Investigating skin penetration depth and shape following needle-free injection at different pressures: A cadaveric study.

BACKGROUND AND OBJECTIVES: The effectiveness of needle-free injection devices in neocollagenesis for treating extended skin planes is an area of active research. It is anticipated that needle-free injection systems will not only be used to inject vaccines or insulin, but will also greatly aid skin rejuvenation when used to inject aesthetic materials such as hyaluronic acid, botulinum toxin, and placental extracts. There has not been any specific research to date examining how materials penetrate the skin when a needle-free injection device is used. In this study, we investigated how material infiltrates the skin when it is injected into a cadaver using a needle-free device. STUDY DESIGN/MATERIALS AND METHODS: Using a needle-free injector (INNOJECTOR™; Amore Pacific, Seoul, Korea), 0.2 ml of 5% methylene blue (MB) or latex was injected into cheeks of human cadavers. The device has a nozzle diameter of 100 µm and produces a jet with velocity of 180 m/s. This jet penetrates the skin and delivers medicine intradermally via liquid propelled by compressed gasses. Materials were injected at pressures of 6 or 8.5 bars, and the injection areas were excised after the procedure. The excised areas were observed visually and with a phototrichogram to investigate the size, infiltration depth, and shape of the hole created on the skin. A small part of the area that was excised was magnified and stained with H&E (×40) for histological examination. RESULTS: We characterized the shape, size, and depth of skin infiltration following injection of 5% MB or latex into cadaver cheeks using a needle-free injection device at various pressure settings. Under visual inspection, the injection at 6 bars created semi-circle-shaped hole that penetrated half the depth of the excised tissue, while injection at 8.5 bars created a cylinder-shaped hole that spanned the entire depth of the excised tissue. More specific measurements were collected using phototrichogram imaging. The shape of the injection entry point was consistently spherical regardless of the amount of pressure used. When injecting 5% MB at 6 bars, the depth of infiltration reached 2.323 mm, while that at 8.5 bars reached 8.906 mm. The area of the hole created by the 5% MB injection was 0.797 mm(2) at 6 bars and 0.242 mm(2) at 8.5 bars. Latex injections reached a depth of 3.480 mm at 6 bars and 7.558 mm at 8.5 bars, and the areas were measured at 1.043 mm(2) (6 bars) and 0.355 mm(2) (8.5 bars). Histological examination showed that the injection penetrated as deep as the superficial musculoaponeurotic system at 6 bars and the masseter muscle at 8.5 bars. CONCLUSION: When injecting material into the skin using a pneumatic needle-free injector, higher-pressure injections result in a hole with smaller area than lower-pressure injections. The depth and shape of skin penetration vary according to the amount of pressure applied. For materials of low density and viscosity, there is a greater difference in penetration depth according to the degree of pressure. Lasers Surg. Med. 48:624-628, 2016. © 2016 Wiley Periodicals, Inc.

Sonographically Guided Posterior Cruciate Ligament Injections: Technique and Validation.

OBJECTIVE: To describe and validate a technique for sonographically guided posterior cruciate ligament (PCL) injections. DESIGN: Prospective, cadaveric laboratory investigation. SETTING: Procedural skills laboratory. SUBJECTS: Eight unembalmed, cadaveric, mid-thigh-knee specimens (4 left knees and 4 right knees) obtained from 4 male and 4 female donors aged 57 to 64 years (mean 60.8 years) with body mass indices of 27.7 to 36.5 kg/m(2) (mean 32 kg/m(2)). METHODS: A 5-2-MHz curvilinear probe and a 22-gauge, 78-mm stainless steel needle was used to inject 2 mL of diluted blue latex into the PCL of each specimen using an in-plane, caudad-to-cephalad approach. At a minimum of 24 hours postinjection, each specimen was dissected to assess the presence and distribution of latex within the PCL. MAIN OUTCOME: Presence and distribution of latex within the PCL. RESULTS: All 8 injections accurately delivered latex throughout the PCL, including the tibial and femoral footprints. In 2 of 8 specimens (25%), a small amount of latex was noted to extend beyond the PCL and into the joint space. No specimens exhibited evidence of needle injury of latex infiltration with respect to the popliteal neurovascular bundle, menisci, hyaline cartilage, or anterior cruciate ligament. CONCLUSIONS: Sonographically guided intraligamentous PCL injections are technically feasible and can be performed with a high degree of accuracy. Sonographically guided PCL injections should be considered for research and clinical purposes to deliver therapeutic agents into the PCL postinjury or postreconstruction.

Sonographically Guided Semimembranosus Bursa Injection: Technique and Validation.

OBJECTIVES: To describe and validate a sonographically guided (SG) semimembranosus (SM) bursa injection technique in an unembalmed cadaveric model. DESIGN: Prospective, cadaveric laboratory investigation. SETTING: Academic institution procedural skills laboratory. SUBJECTS: Ten unembalmed cadaveric thigh-knee-ankle-foot specimens from 4 male and 6 female donors ages 55-92 years (mean 76.2 years) with body mass indices of 15.4-31.8 kg/m(2) (mean 21.9 kg/m(2)). METHODS: A single, experienced operator completed SG SM bursa injections in 10 unembalmed cadaveric knees using 3 mL of diluted colored latex. At a minimum of 2 days after the injection, co-investigators dissected the specimens to assess the distribution of latex with respect to the SM bursa. MAIN OUTCOME: Injections were graded for accuracy as follows: accurate (all latex contained within the SM bursa), accurate with overflow (latex within the SM bursa and extending into regions other than the needle track), or inaccurate (no latex within the SM bursa). RESULTS: All 10 injections (100%) accurately placed latex within the SM bursa and resulted in proximal spread to at least the level of the knee joint. Eight of 10 injections (80%) demonstrated minimal (<1 mL) extrabursal flow without extension into the intra-articular space. No neurovascular injury occurred in any specimen. CONCLUSIONS: SG SM injections are feasible and accurate and may be considered for diagnostic and therapeutic injections in patients with suspected distal SM disorders. Injection volumes less than 3 mL should be considered to reduce extrabursal spread as clinically indicated.

Evaluation of brachial plexus fascicles involvement on infraclavicular block: unfixed cadaver study.

BACKGROUND AND OBJECTIVES: This study shows how the diffusion of the anesthetic into the sheath occurs through the axillary infraclavicular space and hence proves the efficacy of the anesthetic block of the brachial plexus, and may thereby allow a consolidation of this pathway, with fewer complications, previously attached to the anesthesia. MATERIALS AND METHODS: 33 armpits of adult cadavers were analyzed and unfixed. We injected a solution of neoprene with latex dye in the infraclavicular space, based on the technique advocated by Gusmão et al., and put the corpses in refrigerators for three weeks. Subsequently, the specimens were thawed and dissected, exposing the axillary sheath along its entire length. RESULTS AND DISCUSSION: Was demonstrated involvement of all fasciculus of the plexus in 51.46%. In partial involvement was 30.30%, 18.24% of cases the acrylic was located outside the auxiliary sheath involving no issue. CONCLUSIONS: The results allow us to establish the infraclavicular as an effective and easy way to access plexus brachial, because the solution involved the fascicles in 81.76% partially or totally, when it was injected inside the axillary sheath. We believe that only the use of this pathway access in practice it may demonstrate the efficiency.

Factors affecting the anthelmintic efficacy of papaya latex in vivo: host sex and intensity of infection.

The development of plant-derived cysteine proteinases, such as those in papaya latex, as novel anthelmintics requires that the variables affecting efficacy be fully evaluated. Here, we conducted two experiments, the first to test for any effect of host sex and the second to determine whether the intensity of the worm burden carried by mice would influence efficacy. In both experiments, we used the standard C3H mouse reference strain in which papaya latex supernatant (PLS) consistently shows >80 % reduction in Heligmosomoides bakeri worm burdens, but to broaden the perspective, we also included for comparison mice of other strains that are known to respond more poorly to treatment with papaya latex. Our results confirmed that there is a strong genetic influence affecting efficacy of PLS in removing adult worm burdens. However, there was no effect of host sex on efficacy (C3H and NIH) and no effect of infection intensity (C3H and BALB/c). These results offer optimism that plant-derived cysteine proteinases (CPs), such as these from papaya latex, can function as effective anthelmintics, with neither host sex nor infection intensity presenting further hurdles to impede their development for future medicinal and veterinary usage.

Sonographically Guided Anterior Cruciate Ligament Injection: Technique and Validation.

OBJECTIVE: To describe and validate a practical technique for sonographically guided anterior cruciate ligament (ACL) injections. DESIGN: Prospective, cadaveric laboratory investigation. SETTING: Procedural skills laboratory in a tertiary medical center. SUBJECTS: Ten unembalmed, cadaveric mid-thigh-knee-ankle foot specimens (5 left knees and 5 right knees; 5 male and 5 female) from 10 donors aged 76 to 93 years (mean 85.6 years) with body mass indices of 17.6 to 42.2 kg/m(2) (mean 28.8 kg/m(2)). METHODS: A single, experienced operator used a 22-gauge, 63.5-mm stainless steel needle and a 12-3-MHz linear transducer to inject 1.5 mL of diluted colored latex into the ACLs of 10 unembalmed cadaveric specimens via an in-plane, caudad-to-cephalad approach, long axis to the ACL. At a minimum of 24 hours postinjection, specimens were dissected, and the presence and distribution of latex within the ACL assessed by a study co-investigator. MAIN OUTCOME: Presence and distribution of latex within the ACL. RESULTS: All 10 injections accurately delivered latex into the proximal (femoral), midsubstance, and distal (tibial) portions of the ACL. No specimens exhibited evidence of needle injury or latex infiltration with respect to the menisci, hyaline cartilage, or posterior cruciate ligament. CONCLUSIONS: Sonographically guided intra-ligamentous ACL injections are technically feasible and can be performed with a high degree of accuracy. Sonographically guided ACL injections could be considered for research and clinical purposes to directly deliver injectable agents into the healing ACL postinjury or postreconstruction.

Morphometric and high resolution scanning electron microscopy analysis of low-level laser therapy and latex protein (Hevea brasiliensis) administration following a crush injury of the sciatic nerve in rats.

This study evaluated the effect of low-level laser therapy (LLLT; 15 J/cm(2)) and a latex protein (F1) on a crush injury of the sciatic (ischiadicus) nerve. Seventy-two rats (male, 250 g) were divided into 6 groups: CG, control; EG, exposed nerve; IG, injured nerve without treatment; LG, injured nerve with LLLT; HG, injured nerve with F1; and LHG, injured nerve with LLLT and F1. After 4 or 8 weeks, the animals were euthanized and samples of the sciatic nerve were collected for morphometric and high-resolution scanning electron microscopy (HRSEM) analysis. After 4 weeks, the morphometry revealed improvements in the treated animals, and the HG appeared to be the most similar to the CG; after 8 weeks, the injured groups showed improvements compared to the previous period, and the results of the treatment groups were more similar to one another. At HRSEM after 4 weeks, the treated groups were similar and showed improvement compared to the IG; after 8 weeks, the LHG and HG had the best results. In conclusion, the treatments resulted in improvement after the nerve injury, and this recovery was time-dependent. In addition, the use of the F1 resulted in the best morphometric and ultrastructural findings.

Sonographically guided sternoclavicular joint injection: description of technique and validation.

OBJECTIVES: The primary purpose of this investigation was to describe and validate a sonographically guided technique for injecting the sternoclavicular joint (SCJ) using a cadaveric model. METHODS: A single experienced operator (J.S.) completed 13 sonographically guided SCJ injections on 7 unembalmed cadaveric specimens (4 male and 3 female) using an out-of-plane, caudad-to-cephalad technique to place 1 mL of diluted blue latex into the joint. Within 72 hours, study coinvestigators dissected each specimen to determine the injectate location. RESULTS: All 13 injections accurately placed latex into the SCJ with a predilection for the clavicular side (accuracy, 100%; 95% confidence interval, 73%-100%). Three injections (23%) placed all latex on the clavicular side of the SCJ in the presence of a complete intra-articular disk. Dissection revealed incomplete degenerated disks in the remaining 10 joints. Seven of these injections (54%) clearly placed more than 80% of the latex on the clavicular side, whereas the remaining 3 injections (23%) showed nearly equal latex distribution between the clavicular and sternal sides. No injection resulted in neurovascular injury or extracapsular flow. CONCLUSIONS: Sonographically guided SCJ injections can be considered in the diagnosis and management of patients presenting with medial shoulder pain syndromes and, using the technique described herein, have a predilection to target the clavicular portion of the joint. In younger patients with possible complete intra-articular disks or in patients with sternal-side conditions, practitioners should consider confirming sternal-side flow after injection or attempt to specifically target the sternal side of the joint.

Application of a low-level laser therapy and the purified protein from natural latex (Hevea brasiliensis) in the controlled crush injury of the sciatic nerve of rats: a morphological, quantitative, and ultrastructural study.

This study analyzed the effects of a low-level laser therapy (LLLT, 15 J/cm(2), 780 nm wavelength) and the natural latex protein (P1, 0.1%) in sciatic nerve after crush injury (15 Kgf, axonotmesis) in rats. Sixty rats (male, 250 g) were allocated into the 6 groups (n = 10): CG-control group; EG-nerve exposed; IG-injured nerve without treatment; LG-crushed nerve treated with LLLT; PG-injured nerve treated with P1; and LPG-injured nerve treated with LLLT and P1. After 4 or 8 weeks, the nerve samples were processed for morphological, histological quantification and ultrastructural analysis. After 4 weeks, the myelin density and morphological characteristics improved in groups LG, PG, and LPG compared to IG. After 8 weeks, PG, and LPG were similar to CG and the capillary density was higher in the LG, PG, and LPG. In the ultrastructural analysis the PG and LPG had characteristics that were similar to the CG. The application of LLLT and/or P1 improved the recovery from the nerve crush injury, and in the long term, the P1 protein was the better treatment used, since only the application of LLLT has not reached the same results, and these treatments applied together did not potentiate the recovery.

Sonographically guided deep plantar fascia injections: where does the injectate go?

OBJECTIVES: To determine the distribution of sonographically guided deep plantar fascia injections in an unembalmed cadaveric model. METHODS: A single experienced operator completed 10 sonographically guided deep plantar fascia injections in 10 unembalmed cadaveric specimens (5 right and 5 left) obtained from 6 donors (2 male and 4 female) aged 49 to 95 years (mean, 77.5 years) with a mean body mass index of 23.2 kg/m(2) (range, 18.4-26.3 kg/m(2)). A 12-3-MHz linear array transducer was used to direct a 22-gauge, 38-mm stainless steel needle deep to the plantar fascia at the anterior aspect of the calcaneus using an in-plane, medial-to-lateral approach. In each case, 1.5 mL of 50% diluted colored latex was injected deep to the plantar fascia. After a minimum of 72 hours, study coinvestigators dissected each specimen to assess injectate placement. RESULTS: All 10 injections accurately placed latex adjacent to the deep side of the plantar fascia at the anterior calcaneus. However, the flexor digitorum brevis (FDB) origin from the plantar fascia variably limited direct latex contact with the plantar fascia, and small amounts of latex interdigitated with the FDB origin in 90% (9 of 10). In all 10 specimens, latex also covered the traversing first branch of the lateral plantar nerve (FBLPN, ie, Baxter nerve) between the FDB and quadratus plantae muscles. No latex was found in the plantar fat pad or plantar fascia in any specimen. CONCLUSIONS: Sonographically guided deep plantar fascia injections reliably deliver latex deep to the plantar fascia while avoiding intrafascial injection. However, the extent of direct plantar fascia contact is variable due to the intervening FDB. On the contrary, the traversing FBLPN is reliably covered by the injection. Deep plantar fascia injections may have a role in the management of refractory plantar fasciitis, particularly following failed superficial perifascial or intrafascial injections, in cases of preferential deep plantar fascia involvement, or when entrapment/irritation of the distal FBLPN is suspected.

Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex.

CONTEXT: Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragão". Its red latex is used traditionally for treating ulcers, diabetes and cancer. OBJECTIVE: To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. MATERIAL AND METHODS: Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. RESULTS: Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ± 1.84 and 1527.41 ± 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC50 = 169.0 ± 1.8 and 187.0 ± 2.2 µg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. DISCUSSION AND CONCLUSION: These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.

Testicular biodistribution of 450 nm fluorescent latex particles after intramuscular injection in mice.

The significant expansion in the use of nanoparticles and submicron particles during the last 20 years has led to increasing concern about their potential toxicity to humans and particularly their impact on male fertility. Currently, an insufficient number of studies have focused on the testicular biodistribution of particles. The aim of our study was to assess the distribution of 450 nm fluorescent particles in mouse testes after intramuscular injection. To this end, testes were removed from 5 groups of 3 mice each at 1 h (H1), 4 days (D4), 21 days (D21), 45 days (D45) and 90 days (D90) after the injection of 7.28 × 109 particles in the tibialis anterior muscles of each mouse. We examined histological sections from these samples by epifluorescence microscopy and confocal microscopy and identified testicular biodistribution of a small number of particles in groups H1, D4, D21, D45 and D90. Using CD11b immunostaining, we showed that particles were not carried into the testis by macrophages. The intratesticular repartition of particles mainly followed testicular vascularization. Finally, we found some particles in seminiferous tubules but could not determine if the blood-testis barrier was crossed.

Latex immunotherapy: state of the art.

OBJECTIVE: Latex allergy remains a significant problem, especially among certain professional categories, and specific immunotherapy has been suggested as a suitable therapeutic option. The objective of the this article is to review the available literature on clinical trials of specific immunotherapy in latex allergy. DATA SOURCES: Literature databases (PubMed, Embase, Google Scholar) were searched for latex immunotherapy clinical trials. STUDY SELECTIONS: Clinical trials (either open or randomized controlled) using subcutaneous or sublingual immunotherapy with latex extracts were selected. Only articles published in English in peer-reviewed journals were considered. Case reports quoted in the clinical trials were also described, when pertinent. RESULTS: Eleven clinical trials (3 with subcutaneous and 8 with sublingual immunotherapy) were identified. Two of the 3 randomized trials of subcutaneous immunotherapy reported some benefit in adults but a remarkable occurrence of side effects. Concerning sublingual immunotherapy (SLIT), there were 6 randomized placebo-controlled (1 in children), 1 randomized open, and 1 open trials. All but 1 trial reported positive results, and the safety profile was overall superior to injection immunotherapy. The overall quality of the study was moderate, and the number of subjects studied was low. CONCLUSION: Although guidelines do not consider allergy to latex as an accepted indication to desensitization, SLIT can be offered, in addition to symptomatic treatment, to selected patients, when avoidance measures are not feasible or effective.