In vitro evaluation of the percutaneous absorption of progesterone in anhydrous permeation-enhancing base using the Franz skin finite dose model and mass spectrometry.

Progesterone is used for hormone replacement therapy through various routes of administration. This study was conducted to (a) evaluate the stability of progesterone in a proprietary anhydrous permeation-enhancing base (APEB) and the efficiency of its skin permeation, and (b) determine the appropriateness of mass spectrometry as a method of analysis for permeated progesterone. Using a proven stability-indicating ultra-performance liquid chromatographic method, the compounded hormone (100 mg progesterone/g APEB gel) was determined to be physically and chemically stable at room temperature for six months. Skin permeation analysis using the Franz skin finite dose model and mass spectrometry imaging showed an optical density of 1699 for the permeated progesterone compounded in APEB and 550 for the permeated progesterone in a water containing VBC, which is a statistically significant different (P = 0.029). The study suggests that APEB can be used as a compounding base for effective skin permeation of progesterone, and mass spectrometry is a reliable method for visualization and quantitative analysis of permeated progesterone.

Evaluation of the in vitro human skin percutaneous absorption of ketoprofen in topical anhydrous and aqueous gels.

BACKGROUND: Ketoprofen is a nonsteroidal anti-inflammatory drug used for the treatment of acute and chronic pain associated with inflammatory conditions. This study aims to evaluate the in vitro percutaneous absorption of ketoprofen 10% formulated in proprietary anhydrous and aqueous gels using the Franz skin finite dose model. MATERIALS AND METHODS: The anhydrous gel was initially characterized for cytotoxicity using EpiDerm skin tissue model by cell proliferation assay and Western blot analysis. The Ultra Performance Liquid Chromatography method for measuring ketoprofen was validated and the stability of ketoprofen 10% in the anhydrous gel formulation was evaluated at 5°C and 25°C for 181 days. The percutaneous absorption of ketoprofen was determined using donated human skin. The tissue sections were mounted within Franz diffusion cells. A variable finite dose of each ketoprofen formulation in either anhydrous or aqueous gel was applied to the skin sections and receptor solutions were collected at various time points. RESULTS: Cell proliferation assay showed minimal cell death when EpiDerm skin tissue was exposed to the anhydrous gel for 24 h; the levels of protein markers of cell proliferation were not affected after 17-h exposure. Ketoprofen was stable in the anhydrous gel when stored at 5°C and 25°C. When compounded in the anhydrous and aqueous gels, ketoprofen had mean flux rate of 2.22 and 2.50 µg/cm2 /h, respectively, after 48 h. The drug was distributed to the epidermis and dermis sections of the skin. Both the anhydrous and aqueous gels facilitated the percutaneous absorption of ketoprofen without statistically significant differences. CONCLUSION: The anhydrous gel can be used as a base to facilitate the transdermal delivery of ketoprofen. Although the anhydrous and aqueous gels can deliver a similar amount of ketoprofen, the anhydrous gel (water activity below 0.6) allows for extended default beyond-use-date of compounding preparations.

Evaluation of a compounding phospholipid base for the percutaneous absorption of high molecular weight drugs using the Franz finite dose model.

BACKGROUND: Permeation-enhancing compounding bases are aimed to facilitate the penetration of the active pharmaceutical ingredients (APIs) across the skin barrier. OBJECTIVES: The purpose of this study was to evaluate the percutaneous absorption of radiolabeled human insulin (14 C-isototpe) when incorporated in a proprietary phospholipid base designed to deliver APIs with high molecular weights (HMW). The aim was not to claim the transdermal delivery of insulin with potential therapeutic applications in diabetes but, instead, to evaluate the ability of the compounding phospholipid base to deliver HMW drugs. METHODS: The percutaneous absorption of 14 C-insulin was determined using human torso skin and the Franz skin finite dose model. Two topical test formulations were prepared for in vitro evaluation: insulin 1% in phospholipid base (standard) and insulin 1% in phospholipid base HMW. The rate of percutaneous absorption (mean flux) and the distribution of 14 C-insulin through the skin were evaluated for both topical test formulations. A two-way ANOVA was used to determine statistical differences. RESULTS: The 14 C-insulin was distributed into the stratum corneum, epidermis and dermis. Mean flux values showed a rapid penetration upon application and the maximum flux was achieved at 30 min, followed by a slow decline. Subsequently, a slower decline was observed for the topical test formulation including the phospholipid base HMW. CONCLUSION: The phospholipid base HMW facilitates the percutaneous absorption of HMW drugs across human cadaver skin and, therefore, it may potentially be a useful option for compounding pharmacists and practitioners when considering the skin for the percutaneous delivery of large drugs.

Profiles of interferon-stimulated genes in multiple tissues and circulating pregnancy-associated glycoproteins and their association with pregnancy loss in dairy cows†.

Pregnancy loss (PL) in lactating dairy cows disrupts reproductive and productive efficiency. We evaluated the expression of interferon-stimulated genes (ISG) in blood leukocytes, vaginal and cervical epithelial cells, luteolysis-related genes, progesterone, and pregnancy-associated glycoprotein (PAG) profiles in lactating dairy cows (n = 86) to gain insight about PL. Expression of ISG on d17, d19, and d21 was greater in cows that maintained the pregnancy (P33) compared to nonpregnant with no PL (NP). Greater ISG differences between groups were observed in the cervix (96.7-fold) than vagina (31.0-fold), and least in blood leukocytes (5.6-fold). Based on individual profiles of ISG and PAG, PL was determined to occur either before (~13%) or after (~25%) d22. For cows with PL before d22, ISG expression was similar on d17 but by d21 was lower and OXTR was greater than P33 cows and similar to NP; timing of luteolysis was similar compared to NP cows suggesting embryonic failure to promote luteal maintenance and to attach to the endometrium (no increase in PAG). For cows with PL after d22, ISG expression was similar to P33 cows on d17, d19, and d21 and luteolysis, when it occurred, was later than NP cows; delayed increase in PAG suggested later or inadequate embryonic attachment. In conclusion, PL before d22 occurred due to embryonic demise/failure to signal for luteal maintenance, as reflected in reduced ISG expression by d21. Alternatively, embryos with PL between d22 and 33 adequately signaled for luteal maintenance (ISG) but had delayed/inadequate embryonic attachment and/or inappropriate luteolysis causing PL.

Analysis of the Physical Characteristics of an Anhydrous Vehicle for Compounded Pediatric Oral Liquids.

The paucity of suitable drug formulations for pediatric patients generates a need for customized, compounded medications. This research study was set out to comprehensively analyze the physical properties of the new, proprietary anhydrous oral vehicle SuspendIt® Anhydrous, which was designed for compounding pediatric oral liquids. A wide range of tests was used, including sedimentation volume, viscosity, droplet size after dispersion in simulated gastric fluid, microscopic examination and content uniformity measurements to evaluate the properties of the anhydrous vehicle. The results showed that the vehicle exhibited consistent physical properties under varying conditions and maintained stability over time. This can be attributed to the unique blend of excipients in its formulation, which not only maintain its viscosity but also confer thixotropic behavior. The unique combination of viscous, thixotropic and self-emulsifying properties allows for rapid redispersibility, sedimentation stability, accurate dosing, potential drug solubility, dispersion and promotion of enhanced gastrointestinal distribution and absorption. Furthermore, the vehicle demonstrated long-term sedimentation stability and content uniformity for a list of 13 anhydrous suspensions. These results suggest that the anhydrous oral vehicle could serve as a versatile base for pediatric formulation, potentially filling an important gap in pediatric drug delivery. Future studies can further investigate its compatibility, stability and performance with other drugs and in different clinical scenarios.

Mental health and well-being of PhilHealth frontline workers

Background@#The mental health and well-being of PhilHealth frontline workers were investigated to inform decision-makers and organizations in developing policies and programs to promote welfare of employees, thereby subsequently improving productivity and service delivery. @*Objectives@#The study aimed to describe the demographic profile of participants and their level of mental health and well-being as well as to determine if a significant relationship exists between the said variables. @*Methodology@#This is descriptive research that gathered respondents’ socio-demographic data. The target population was PhilHealth frontline workers all over the Philippines. Two existing self-report scales were used to measure the mental health and well-being of respondents. Statistical tools were then used to interpret data. @*Results@#The majority of demographic factors were related to mild anxiety levels. The mean scores suggest that ages 20-29 are more anxious than those aged 50 and above. Other findings noted that the position title of Administrative Aide III and place of assignment in PhilHealth Regional Office II and XII showed a severe level of anxiety. Mean scores also showed mild anxiety as the length of years working in the corporation increased. In conclusion, age, years in service and place of assignment have a significant negative impact on participants’ mental health. @*Conclusion@#In conclusion, age, years in service and the place of assignment were the variables found to have a statistically recognizable impact on mental health and well-being of PhilHealth frontline workers. These findings were considered in proposing Mental Health Programs for PhilHealth employees. @*@#

Evaluation of an Anhydrous Permeation-Enhancing Vehicle for Percutaneous Absorption of Hormones.

The efficiency and safety of hormone delivery through the skin partly depend on the appropriate choice of vehicle and the type of formulation. The present study reports the skin cytotoxicity, irritancy, and safety of a newly developed anhydrous permeation-enhancing base (APEB) and the percutaneous absorption of progesterone, testosterone, estriol, and estradiol in APEB formulations. Using the human skin EpiDerm model, cell death was not observed after 4 h of exposure to APEB and was 48% after 24 h, indicating its mild to non-irritating property. APEB did not change the expression level of skin cell proliferation markers including PCNA, MCL-1, iNOS, and NFκB proteins, and apoptosis was minimal after 8-h exposure. The in vivo skin irritation and sensitization evaluation of APEB using a Human Repeat Insult Patch Test showed no adverse reaction of any kind during the course of the study. These results indicate the safety of APEB on skin tissues. The hormone percutaneous absorption was performed using human cadaver abdomen skin tissues and the Franz diffusion system, and hormone concentrations were determined by ELISA. Absorption was observed as early as 2 h of application and accumulated after 24 h to 2851 ± 66 ng/cm2, 2338 ± 594 ng/cm2, 55 ± 25 ng/cm2, and 341 ± 122 ng/cm2 for progesterone, testosterone, estriol, and estradiol, respectively. A steady flux rate of absorption of the hormones was observed within 24 h of application. These results suggest that APEB can be used as a vehicle to deliver these hormones through the skin and into the bloodstream for hormone replacement therapy.

Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Beyond-use Date of Trimix: A Reproducible Stability Study Using Bracketing Design.

Trimix is a widely prescribed penile injection for patients with erectile dysfunction and is only available as a compounded medication. The instability of alprostadil, one of the major ingredients of Trimix, has been a limiting factor in its utilization. There are published stability data for Trimix formulations that have been used to establish a beyond-use-date. However, a robust bracketed study that is shown to be reproducible is highly desirable and meaningful. The purpose of this study was to test the reproducibility of a bracketed stability study when the preparations were made by two different entities to provide beyond-use date information of Trimix preparations that cover a wide range of strengths. A validated stability indicating method was used to compare the stability of a bracketed Trimix - alprostadil 5 µg/mL to 45 µg/mL, papaverine 15 mg/mL to 30 mg/mL, and phentolamine 0.4 mg/mL to 5 mg/mL, and a single-strength preparation containing alprostadil 30 µg/mL, papaverine 30 mg/mL, and phentolamine 2 mg/mL that were compounded and stored following the same methods and conditions, but at two different practice settings. Beyond-use dates of 60 days and 64 days at cold temperature were obtained for the two preparations from two different settings. The consistent results confirmed the reproducibility of the bracketing designs used to determine the beyond-use dates of Trimix. The clinical value of these results stems from the availability of accurate and widely applicable stability data that can be referenced to establish beyond use dates of a number of Trimix preparations with various strength combinations.

Evaluation of the Efficacy and Stability of Compounded Pentoxifylline-containing XemaTop for Psoriasis.

Psoriasis is an inflammation-mediated skin disorder for which an efficacious topical treatment is yet to be identified. A new compounded topical formulation containing 10% pentoxifylline in XemaTop base was recently developed for psoriasis. Prior to its use in humans, an in vitro evaluation was performed to determine its efficacy in attenuating molecular markers associated with psoriasis using a three-dimensional psoriasis tissue model. After 5 days of topical exposure to the formulation, the levels of inflammatory cytokines IL-1ß, IL-6, and GM-CSF decreased by 20%, 94%, and 96%, respectively. The production of pro-collagen type I and fibronectin essential for cellular proliferation was also significantly inhibited with a concomitant thinning of the epidermis. These results suggest that 10% pentoxifylline in XemaTop is efficacious in inhibiting the biomarkers associated with psoriasis. Pentoxifylline in XemaTop was stable within 91 days when stored under refrigerated or ambient conditions. These biochemical and stability studies suggest that 10% pentoxifylline in XemaTop may be evaluated now in psoriasis patients.

In vitro evaluation of Naltrexone HCl 1% Topical Cream in XemaTop™ for psoriasis.

Psoriasis is a multifactorial skin disease involving abnormal cell proliferation and inflammation; an efficacious topical treatment is yet to be identified. A formulation containing 1% Naltrexone HCl in XemaTop™ base was compounded, characterized and evaluated in vitro as a possible treatment for psoriasis. A three-dimensional psoriasis tissue model was exposed to the formulation for 2 or 5 days and analyzed for the level of markers of cellular proliferation, and inflammatory cytokine IL-6. Using immunohistochemical staining, the level of Ki67 protein significantly decreased in the drug-treated tissues. Western blot analysis showed 86% and 53% down-regulation of other proliferation markers PCNA and CYCLIN D1, respectively, after 5-day exposure. The pro-survival Wnt/ß-catenin pathway was compromised as indicated by 57% decrease in the level of ß-CATENIN and down-regulation of its down-stream targets including CYCLIN D1 (decreased by 53%), c-MYC (63%), c-JUN (92%) and MET (96%) proteins. Likewise, the PI3K/AKT/mTOR pathway was significantly inhibited by 1% Naltrexone HCl in XemaTop™, suggesting protein synthesis was affected. The production of IL-6 was inhibited by 70% in drug-treated tissues. These results suggest that the compounded drug is efficacious in down-regulating molecular markers associated with the pathogenesis of psoriasis. Low-dose Naltrexone in XemaTop™ was stable within 180 days when stored under refrigerated or ambient conditions. These results provide a basis for a clinical evaluation of 1% Naltrexone HCl in XemaTop™ in psoriasis patients.

Pediatric Compounding Pharmacy: Taking on the Responsibility of Providing Quality Customized Prescriptions.

Compounding pharmacy has an important role to play in the field of pediatric medicine. These specialized pharmacies can offer solutions to the unique patient needs that arise in the pediatric population. Medication can be tailored to the child to allow better compliance in cases when the commercial product is unable to meet the needs of the patient. For example, a suspension, suppository, or lozenge formulation is sometimes needed when the manufactured products are only offered as solid oral dosage forms. Sensory processing disorder (SPD), patients with food allergies, and specific dietary needs can also be a big challenge for caregivers and practitioners who need alternatives to the commercially available forms. Three example cases are presented to help describe the process of collaboration between the pharmacist, patient, and doctor to solve the patient's needs.

Effects of Compounded Stanford Modified Oral Rinse (MucoLox) on the Survival and Migration of Oral Keratinocytes and Fibroblasts: Implications for Wound Healing.

Several oral rinses are commercially available to alleviate the symptoms of oral mucositis. Prolonged retention of active pharmaceutical ingredients in the oral cavity is a major problem. In this study, we modified the Stanford oral rinse by including a proprietary mucoadhesive polymer called MucoLox, which we hypothesized would improve active pharmaceutical ingredient mucoadhesion. Characterization of this newly compounded oral rinse showed absence of cytotoxicity in human oral keratinocyte and fibroblast cell lines. The compounded formulation significantly stimulated the migration of these two cell lines in Oris Cell Migration Assay plates, better than the reference commercial product Magic mouthwash. Based on this in vitro study, the new Stanford modified oral rinse with MucoLox is safe and may promote healing of oral mucositis.

STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin- and mucosa-derived cell types: implications in neoplastic and inflammatory skin diseases.

BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS: Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

Reversible dilatation of lumbar epidural venous plexus secondary to pelvic venous compression: mimicker of pathology.

Radiculopathy from dilated epidural varices is a rarely recognized phenomenon, and engorged varices may mimic a disc herniation, fistula or mass. We report a case of a distended bladder causing reversible pelvic venous congestion and resultant epidural venous plexus engorgement. We show marked engorgement of the epidural venous plexus and crowding of the cauda equina from a markedly distended bladder with resolution of these findings following bladder decompression. Familiarity with this clinical entity is crucial to avoid misdiagnosis and to prevent potential unnecessary surgical intervention.

Evaluation of the Safety, Cell Migration, and Mucoadhesive Properties of a Mucoadhesive Polymer Blend in Human Oral Mucosa.

The efficacy of active pharmaceutical ingredients (API) in compounded medications for oral mucosa greatly depends on the composition of the base. Here, we assessed the safety, facilitation of cell migration, and mucoadhesive properties of a newly developed mucoadhesive polymer blend (MPB) which contains pullulan, tamarindus indica polysaccharide, and sodium hyaluronate. No cell death was observed when human oral keratinocyte (HOK) and fibroblast (HOrF) cells were exposed to 1% MPB for 24 h. Epithelial cells in a 3D buccal tissue model (EpiOral) were unaffected when exposed to 50% MPB for 20 h whereas 1% Triton X-100 killed 93% cells after 4.5 h. The expressions of cytokines IL1α and IL1ß and cell proliferation markers PCNA, CYCLIN A, and CYCLIN D1 in EpiOral tissue did not increase suggesting that MPB is neither an irritant nor a mitogen. Markers of apoptosis such as cleavage of CASPASES 8/9, upregulation of pro-apoptosis NOXA protein, and downregulation of anti-apoptosis XIAP protein were observed in Triton X-100-treated cells but not in cells exposed to MPB. The migration of HOK and HOrF cells was stimulated by MPB, and the expression of E-CADHERIN in the EpiOral tissues was unaffected. Moreover, MPB showed stronger mucoadhesion on the human EpiOral tissue model compared with a reference product. We conclude that MPB can safely deliver API within the oral mucosa, facilitate cell migration, and may increase drug efficacy through its strong mucoadhesive property.

Characterization of the Percutaneous Absorption of Ketoprofen Using the Franz Skin Finite Dose Model.

OBJECTIVES: Ketoprofen is an analgesic, anti-inflammatory agent commonly used in the management of chronic musculoskeletal pain. The aim of this study is to characterize the percutaneous absorption of 2 ketoprofen formulations (ketoprofen 10% in Pluronic Lecithin Organogel (PLO) and ketoprofen 10% in Lipoderm, referred to as phospholipid base), when applied to the human cadaver trunk skin, in vitro, using the Franz skin finite dose model. PLO and phospholipid base are vehicles used to facilitate the delivery of drugs into and through the skin following topical applications. METHODS: The percutaneous absorption of ketoprofen was evaluated using human cadaver trunk skin from 3 donors. The skin was cut into small sections and cultured within Franz diffusion cells. A variable finite dose of each formulation was then applied to 3 replicate skin sections per donor and receptor solutions were collected at predetermined time points (0, 4, 8, 12, 24, 32, and 48 hr). After the last receptor sample was collected, skin surfaces were washed and split into epidermis and dermis. Collected samples were analyzed using HPLC. RESULTS: Both PLO and phospholipid base were capable of facilitating the absorption of ketoprofen across human cadaver trunk skin. However, ketoprofen, when in phospholipid base, showed higher mean total absorption (p = 0.022) and faster rate of absorption (p < 0.05 at 2, 6, 10, and 18 hr) than when in PLO. CONCLUSION: Chronic musculoskeletal pain can be a major burden for most patients, affecting their lifestyle and reducing overall quality of life. When compared to PLO, phospholipid base has the ability to potentially deliver higher concentrations of ketoprofen to underlying soft tissues and at a more rapid rate. With more ketoprofen at the site of injury, the analgesic and anti-inflammatory effects will likely be enhanced, potentially reducing pain and improving quality of life.

Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model.

OBJECTIVE: This study evaluates the ability of four commonly used analgesics (ketamine HCl, gabapentin, clonidine HCl, and baclofen), when incorporated into two transdermal compounding bases, Lipoderm and Lipoderm ActiveMax, to penetrate human cadaver trunk skin in vitro, using the Franz finite dose model. DESIGN: In vitro experimental study. Methods. Ketamine HCl 5% w/w, gabapentin 10% w/w, clonidine HCl 0.2% w/w, and baclofen 2% w/w were compounded into two transdermal bases, Lipoderm and Lipoderm ActiveMax. Each compounded drug formulation was tested on skin from three different donors and three replicate skin sections per donor. The Franz finite dose model was used in this study to evaluate the percutaneous absorption and distribution of drugs within each formulation. RESULTS: Rapid penetration to peak flux was detected for gabapentin and baclofen at approximately 1 hour after application. Clonidine HCl also had a rapid penetration to peak flux occurring approximately 1 hour after application and had a secondary peak at approximately 40 hours. Ketamine HCl exhibited higher overall absorption rates than the other drugs, and peaked at 6­10 hours. Similar patterns of drug distribution within the skin were also observed using both transdermal bases. CONCLUSIONS: This study suggests that the combination of these 4 analgesic drugs can be successfully delivered transdermally, using either Lipoderm or Lipoderm ActiveMax. Compounded transdermal drug preparations may then provide physicians with an alternative to traditional oral pain management regimens that can be personalized to the specific patient with the potential for enhanced pain control.

Case series: the effectiveness of Fatty acids from pracaxi oil in a topical silicone base for scar and wound therapy.

INTRODUCTION: Wounding affects the integrity of the skin and can ultimately result in skin scarring. Current therapeutic goals of wound treatment focus on the reduction of scar formation and severity. However, scar formation itself varies not only between individuals based on factors such as ethnicity, but also within an individual based on the location of the wound. Therefore, the preparation of customized treatments for individual patients represents an important therapeutic goal in the fields of dermatology and wound healing. The objective of this study was to evaluate the usefulness of fatty acids found in pracaxi oil in a compounded topical anhydrous silicone base for wound and scar therapy. METHODS: Initially, 21 patients with various surgical, traumatic, or burn wounds and scars were enrolled into this case series. Patients applied a compounded topical anhydrous silicone base containing pracaxi oil with or without additional active ingredients, including pentoxifylline, caffeine, tranilast, and mupirocin. Wound/scar photographs taken before and after application of the compounded pracaxi oil topical formulation (with/without additional ingredients) were reviewed and adjudicated by a blinded dermatology reviewer. Improvements in wound size, coloration, and overall appearance before and after treatment were determined. Patient satisfaction was assessed after application of compounded topical formulation using a self-report questionnaire distributed at the time of dispensing. RESULTS: A total of seven patients were considered available for analysis and were included in the study. In all seven cases, patients reported improvement in scar and wound attributes, including scar and wound size, severity, color, and pain associated with the scar or wound after application of the compounded medicine. On average, patients rated their satisfaction with treatment highly, with a mean score of 10 on a rating scale of 1-10. Retrospective review of wound/scar photographs demonstrated clinically relevant improvements in wound attributes as assessed by a dermatologist. Six of the seven wounds examined were considered "much improved" from baseline. CONCLUSIONS: Application of a compounded anhydrous silicone base containing pracaxi oil alone or in combination with other active substances led to considerable improvements in wound healing and scar attributes and is a potentially useful option in the treatment of surgical, traumatic, or burn wounds and scars.

Intracranial causes of ophthalmoplegia: the visual reflex pathways.

The gathering of visual information is a complex process that relies on concerted movements of the eyes, and cranial nerves II-VIII are at least partially involved in the visual system. The cranial nerves do not function in isolation, however, and there are multiple higher-order cortical centers that have input into the cranial nerves to coordinate eye movement. Among the functions of the cortical reflex pathways are (a) controlling vertical and horizontal gaze in response to vestibular input to keep the eyes focused on an object as the head moves through space, and (b) controlling rapid, coordinated eye movement to a new visual target (saccades). There are also reflex pathways connecting the cranial nerves involved in vision that produce consensual blinking of the eyes in response to corneal stimulation of one eye and consensual pupillary constriction in response to light input on one pupil. A variety of intracranial pathologic conditions, including benign and malignant neoplasms, infection, trauma, autoimmune diseases, vascular anomalies, degenerative diseases, and inherited-congenital disorders, can disrupt the cranial nerves and visual reflex pathways. This disruption can manifest in myriad ways-for example, as extraocular muscle paresis, afferent pupillary defect, oculosympathetic paresis (Horner syndrome), internuclear ophthalmoplegia, dorsal midbrain (Parinaud) syndrome, or loss of the corneal reflex. Knowledge of the function and anatomy of the cranial nerves and visual reflex pathways, coupled with selection of the proper magnetic resonance pulse sequence, will allow the radiologist to order appropriate imaging of the involved cranial nerve or visual reflex pathway based on the patient's symptoms and thereby play an essential role in establishing the diagnosis and planning appropriate therapy.