Compatibility of Cetirizine Hydrochloride, Dutasteride, Hydrocortisone Acetate, Nicotinamide, Progesterone, and Pyridoxine Hydrochloride in TrichoSolTM, A Natural Vehicle for Hair Solutions.

Compounding pharmacies commonly use ready-to-use vehicles such as TrichoSolTM to produce hair solutions for alopecia. However, chemical and microbiological compatibility are paramount to be determined so those can be safely implemented as the vehicle of choice. This study aimed to assess the physical-chemical and microbiological stabilities of selected active pharmaceutical ingredients in TrichoSolTM. For that, HPLC analyses and Antimicrobial Effectiveness Testing were conducted in bracketed studies. The beyond-use dates (BUDs) found were: 180 days for cetirizine hydrochloride 0.5%-2.0%, dutasteride 0.1%, hydrocortisone acetate 0.5%, nicotinamide 0.25%-0.50%, progesterone 1.0%, and pyridoxine hydrochloride 0.25%-5.0%. BUDs of 150 days were observed for hydrocortisone acetate 1.0%, 120 days for Dutasteride 0.25%, and 90 days for progesterone 2.5%.

Compatibility of Caffeine Clobetasol Propionate Dutasteride Nicotinamide and Progesterone in TrichoFoam™, a Natural Vehicle for Hair Foams.

BACKGROUND: Alopecia is a chronic dermatological disorder affecting men and women worldwide. Given the high incidence and significant impact on patients' well-being, options for managing and treating alopecia are essential. Topical available options remain limited and oral products may result in adverse effects. TrichoFoam™ is a ready-to-use foaming vehicle developed for compounding pharmacies and formulated with gentle, non-irritating, and sensory-pleasant ingredients. OBJECTIVE: The purpose of this study was to assess topical foams' physicochemical and microbiological stabilities of formulations compounded with TrichoFoam™ as the ready-touse vehicle. METHODS: HPLC analyses were conducted in a bracketed study covering concentrations of 0.1% to 2.0% of caffeine, 0.01% to 0.1% of clobetasol propionate, 0.1% to 0.25% of dutasteride, 0.25% to 0.50% of nicotinamide, and 0.25% to 2.5% of progesterone compounded with TrichoFoam™. Antimicrobial Effectiveness Testing was conducted at the beginning and end of the studies. RESULTS: Most formulations presented a beyond-use date of at least 90-180 days, except for clobetasol propionate, which showed compatibility for 14 days, and dutasteride 0.25%, which showed a BUD of 30 days. CONCLUSION: This validates the stability of the active pharmaceutical ingredients from different pharmacological classes with TrichoFoam™, suggesting that this ready-to-use vehicle can be an excellent alternative for personalized alopecia treatment.

The Burden of Care of Nasoalveolar Molding: An Institutional Experience.

Nasoalveolar molding (NAM) is an early presurgical intervention to facilitate primary cleft lip repair by reducing cleft severity and improving labial and nasal form. However, it continues to be associated with the burden of care that influences access and completion of therapy. The authors, therefore, aim to determine the burden of care of NAM therapy for families seeking treatment at a high-volume urban cleft center. A retrospective study of all patients undergoing primary cleft repair between 2012 and 2020 was performed. Patients were grouped based on whether or not NAM therapy was offered. Variables including physical, psychosocial, and financial factors were assessed. Two hundred and thirty patients underwent primary cleft repair between 2012 and 2020. Of these, 176 patients were indicated for NAM, with 4% discontinuing, and 54 patients did not undergo NAM. The 169 patients who completed NAM had a mean duration of treatment of 13.6±8.8 wks consisting of 15±6 scheduled NAM adjustment visits and 1±1 unscheduled visit made urgently to assess caregiver concerns. The mean travel distance was 28.6±37.1 miles. Eighty-four percent of caregivers were married, and 16% did not have English as a primary language. Though 57% had private insurance, 43% of patients received charity support for their treatment. NAM is a finite presurgical intervention that requires caregivers to participate in patient care for approximately three months of their early life. The decision to pursue NAM should be considered alongside the burden of care for caregivers to complete treatment.

Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.

Hoof lesions in partly housed pasture-based dairy cows.

Lameness is a symptom of a painful disorder affecting the limbs, which impacts dairy cow welfare and productivity. Lameness is primarily caused by hoof lesions. The prevalence of different lesion types can differ depending on environmental conditions and farm management practices. The aims of this observational study were to establish the cow-level and herd-level lesion prevalence during both housing and grazing periods in a partly housed, pasture-based system, establish the prevalence of lesions always associated with pain ("alarm" lesion), identify the lesions associated with a higher lameness score, determine relationships between lesions, and identify risk factors for digital dermatitis. On 98 farms during the grazing period and on 74 of the same farms during the housing period, every cow was lameness scored (0-3 lameness scoring scale), and the hind hooves of lame cows (score 2 and 3) were examined (maximum 20 cows per visit) and the prevalence of each lesion type recorded. To gather data on potential predictors for the risk factor analysis, a questionnaire with the farmer was conducted on lameness management practices and infrastructure measurements were taken at each visit. Cow-level data were also collected (e.g., parity, breed, milk yield, and so on). Noninfectious lesions were found to be more prevalent than infectious lesions in this system type. The most prevalent lesion types during both grazing and housing periods were white line separation, sole hemorrhages and overgrown claws; all remaining lesions had a cow-level prevalence of less than 15%. The cow-level prevalence of alarm lesions was 19% during the grazing period and 25% during the housing period; the most prevalent alarm lesion was sole ulcers during both periods. We found significantly more foreign bodies within the hoof sole (grazing = 14%, housing = 7%) and overgrown claws (grazing = 71%, housing = 55%) during the grazing period compared with the housing period. Cows with foul of the foot, sole ulcer, white line abscess, toe necrosis or an amputated claw had higher odds of being more severely lame, compared with mildly lame. The strongest correlation between lesions were between toe necrosis and digital dermatitis (r = 0.40), overgrown claws and corkscrew claws (r = 0.33), and interdigital hyperplasia and digital dermatitis (r = 0.31) at herd level. At the cow level, the strongest correlation was between overgrown claws and corkscrew claws (r = 0.27), and digital dermatitis and heel erosion (r = 0.22). The farmers' perception of the presence of digital dermatitis (and lameness) was significantly correlated with the actual presence of digital dermatitis recorded. Additional risk factors for the presence of digital dermatitis were cow track and verge width near the collecting yard, and stone presence on the cow tracks. Results from this study help further our understanding of the causes of lameness in partly housed, pasture-based dairy cows, and can be used to guide prevention and treatment protocols.

Do We Need Support in Prepectoral Breast Reconstruction? Comparing Outcomes with and without ADM.

BACKGROUND: The majority of two-stage prepectoral breast reconstruction has been described utilizing acellular dermal matrix (ADM). Although reports of prepectoral breast reconstruction without ADM exist, there is a paucity of comparative studies. METHODS: A single-institution retrospective review was performed of consecutive patients undergoing immediate prepectoral two-stage breast reconstruction with tissue expanders from 2017 to 2019. Short-term reconstructive and aesthetic complications were compared between cases that utilized ADM for support and those that did not. RESULTS: In total, 76 cases (51 patients) were identified, of which 35 cases utilized ADM and 41 did not. Risk factors and demographics were similar between the two cohorts with the exception of body mass index, which was higher in the ADM cohort (29.3 versus 25.4, P = 0.011). Average follow-up length was also longer in patients who received ADM (20.3 versus 12.3 months, P < 0.001). Intraoperative expander fill was higher in patients who did not receive ADM (296.8 cm3 versus 151.4 cm3, P < 0.001) though final implant size was comparable in both cohorts (P = 0.584). There was no significant difference in the rate of any complication between the ADM and no ADM cohorts (25.7% versus 17.1%, respectively P = 0.357), including major mastectomy flap necrosis (P = 0.245), major infection (P = 1.000), seroma (P = 0.620), expander explantation (P = 1.000), capsular contracture (P = 1.000), implant dystopia (P = 1.000), and rippling (P = 0.362). CONCLUSIONS: Immediate two-stage prepectoral breast reconstruction with tissue expanders has comparable rates of short-term complications with or without ADM support. Safety of prepectoral expander placement without ADM may warrant more selective ADM use in these cases.

Compatibility of Estradiol, Estriol, Estrone, Progesterone, and Testosterone Single Formulation in Fitalite, Versatile, or HRT Supreme Cream Base.

In this work, we focus on three ready-to-use vehicles: Fitalite, Versatile, and HRT Supreme Cream Base. Fitalite is a natural, light, hydrophilic gel-cream that contains vitamin E and oil bodies from plant sources (phytosomes), providing antioxidant and skinmoisturizing properties. Versatile is a vanishing oil-inwater cream base which retains its consistency with a broad range and high concentrations of active pharmaceutical ingredients, dermaceutical ingredients, and solvents. Finally, HRT Supreme Cream Base is a paraben-free, dye-free, fragrance-free O/W emulsion base, formulated with a complex of botanical oils to soothe and provide moisture to dry and sensitive skin. In the current study, we evaluated the beyond-use date of formulations containing estradiol, estriol, estrone, progesterone, and testosterone in combination, compounded with these three vehicles. Validated, stability-indicating high-performance liquid chromatography methods were used throughout a 180-day period. A beyond-use date of 180 days was observed for all vehicles stored both at refrigerated and at room temperature. The combination of five ingredients represents a worst-case scenario since there are more possibilities of cross reactions. Therefore, we expect the same or greater stability as individual ingredients are removed from the tested formulation. The extended beyond-use dates provide convenience for both the compounding pharmacist and the patient.

Postulated Adjuvant Therapeutic Strategies for COVID-19.

The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, twelve therapeutic agents that could play a role in prophylaxis or improvement of the COVID-19-associated symptoms (as add-on substances) are discussed. Agents were identified based on their known pharmacologic mechanism of action in viral and/or nonviral fields and are postulated to interact with one or more of the seven known mechanisms associated with the SARS-CoV-2 virus: (i) regulation of the immune system; (ii) virus entrance in the cell; (iii) virus replication; (iv) hyperinflammation; (v) oxidative stress; (vi) thrombosis; and (vii) endotheliitis. Selected agents were immune transfer factor (oligo- and polypeptides from porcine spleen, ultrafiltered at <10 kDa; Imuno TF®), anti-inflammatory natural blend (Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis; Miodesin®), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax®). This review gives the scientific background on the hypothesis that these therapeutic agents can act in synergy in the prevention and improvement of COVID-19-associated symptoms.

Ex Vivo Evaluation of Intravaginal Progesterone and Testosterone to Treat the Luteal-phase Deficiency and Vaginal Atrophy.

The purpose of this study was to evaluate the transmucosal permeation of progesterone and testosterone using Pentravan as its vehicle for vaginal delivery. Progesterone deficiency is a hormone imbalance that could lead to luteal-phase deficiency, which is a common problem in assisted reproductive technologies. Testosterone has been explored for treating postmenopausal symptoms, such as vaginal atrophy. The ex vivo experiments were performed using porcine vaginal mucosa and phosphate buffered saline + 0.5% 2-hydroxypropyl-ß-cyclodextrin as the receptor media, which was later quantified through high-performance liquid chromatography. The percentage of the permeated drug was 0.4% and 20.3% for progesterone and testosterone, respectively. The permeation studies revealed that testosterone formulated with Pentravan is potentially effective in reaching the bloodstream and acts locally, whereas progesterone was mostly retained in the mucosa.

Type of oral solid medication packaging and medication preparation time in nursing homes: A direct observation study.

WHAT IS KNOWN AND OBJECTIVE: Medication administration is a substantial portion of the workday in nursing homes, with the medication preparation step being the most time-consuming. However, little is known about how medication preparation time is affected by the type of packaging used for oral solid medications (ie, tablets/capsules). We examined the effects of two types of packaging. As fewer steps are associated with strip packaging compared to bingo card packaging, we hypothesized that the increase in medication preparation seconds per resident with each additional oral solid medication would be smaller when strip packaging was used. METHODS: A total of 430 medication preparations conducted by eight nurses during the regularly scheduled morning medication administration period in two nursing homes-using strip packaging and bingo card packaging, respectively-were observed. Each medication preparation observation was matched to its corresponding medication administration record and observations averaged across resident. Using the resident sample (N=149), we estimated three regression models (adjusting the standard errors for the clustering of resident by nurse). The first model regressed medication preparation seconds on the number of oral solid medications. The second model added the type of packaging used and the control variables (type of unit [long-term care, post-acute care], the number of one-half pills and the dosage form diversity in the preparation). To test our hypothesis, the third model added an interaction term between the number of oral solid medications and the type of packaging used. RESULTS AND DISCUSSION: As hypothesized, all else equal, the number of oral solid medications tended to increase medication preparation time per resident in both nursing homes, but the increase was smaller in the strip packaging nursing home (P<.05). Each additional oral solid medication in the bingo card packaging nursing home increased medication preparation by an average of 13 seconds (b=13.077), whereas each oral solid medication administered in the strip packaging nursing home increased medication preparation by an average of only 8 seconds (13.077-5.092=7.985). This is a difference on average of about 5 seconds per oral solid medication. WHAT IS NEW AND CONCLUSION: To our knowledge, we were the first to examine the effect of type of oral solid medication packaging on medication preparation time in nursing homes. Type of packaging matters. The time saved using strip packaging (vs bingo card packaging) has implications for quality of care and the movement towards person-centred care in the nursing home sector. Nurses (or other staff tasked with medication preparation) in nursing homes using strip packaging potentially have more time to devote to nurturing a relationship with the resident. However, time saved in medication preparation by strip packaging is counterproductive if a serious error results. Thus, future studies should investigate the effects of type of packaging on medication preparation errors.

Aqueous humor endothelin-1 and total retinal blood flow in patients with non-proliferative diabetic retinopathy.

PurposeThe purpose of this study was to determine the association between aqueous ET-1 levels and total retinal blood flow (TRBF) in patients with non-insulin-dependent type 2 diabetes mellitus (T2DM) and early non-proliferative diabetic retinopathy (NPDR).Patients and methodsA total of 15 age-matched controls and 15 T2DM patients with NPDR were recruited into the study. Aqueous humor (~80-120 µl) was collected before cataract surgery to measure the levels of ET-1 using suspension multiplex array technology. Four weeks post surgery, six images were acquired to assess TRBF using the prototype RTVue Doppler FD-OCT (Optovue, Inc., Fremont, CA, USA) with a double circular scan protocol. At the same visit, forearm blood was collected to determine plasma glycosylated hemoglobin (A1c) levels.ResultsAqueous ET-1 was significantly elevated in the NPDR group compared with the control group (3.5±1.8 vs 2.2±0.8, P=0.02). TRBF was found to be significantly reduced in the NPDR group compared with the control group (34.5±9.1 vs 44.1±4.6 µl/min, P=0.002). TRBF and aqueous ET-1 were not correlated within the NPDR group (r=-0.24, P=0.22). In a multivariate analysis, high A1c was associated with reduced TRBF and aqueous ET-1 levels across control and NPDR groups (P<0.01).ConclusionAqueous ET-1 levels were increased while TRBF was reduced in patients with NPDR compared with the control group. Although not directly associated, the vasoconstrictory effects of ET-1 are consistent with a reduced TRBF observed in early DR. ET-1 dysregulation may contribute to a reduction in retinal blood flow during early DR.

Transfusion in adults: 10-year survival of red cell, plasma and platelet recipients following transfusion.

OBJECTIVE: To determine the long-term survival of adult recipients (>16 years) transfused with red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) in England and Wales. STUDY DESIGN AND METHODS: The EASTR study (Epidemiology and Survival of Transfusion Recipients) was a national multi-centre epidemiological study with cross-sectional sampling from 29 representative hospitals in England supplied by NHS Blood and Transplant (NHSBT). Three separate groups of RBC (n = 9142), FFP (n = 4232) and PLT (3584) recipients were sampled over 1 year (1 October 2001-30 September 2002), with prospective survival monitoring for 10 years. This study presents the data for adult recipients (>16 years of age). RESULTS: The median age interquartile range (IQR) of adult transfusion recipients was RBC 70 (54-79), FFP 66 (51-76), PLT 62 (48-72). The 10-year survival for adult RBC, FFP and PLT recipients was highest for RBC recipients at 36% confidence interval (CI 35-37%, n = 8675), compared with 30% for both FFP (CI 29-32%, n = 3849) and PLT (CI 28-30%, n = 3110) recipients. In all groups, post-transfusion survival decreased with age, and a risk-adjusted analysis showed that reason for transfusion, transfusion type (surgical or medical) and cancer diagnosis (presence or absence) were all significantly associated with survival. Older patients with cancer receiving a medical rather than surgical transfusion had the highest hazard of death. CONCLUSION: This study shows that survival following transfusion in England is broadly similar to that reported in other wealthy nations. More than 70% of recipients die within 10 years of transfusion, but long-term survival is common in younger patients (>80% 10-year survival in RBC recipients aged 16-39 years).

Transfusion in children: epidemiology and 10-year survival of transfusion recipients.

OBJECTIVE: To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post-transfusion survival. STUDY DESIGN AND METHODS: The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi-centre epidemiological study with prospective survival monitoring. Cross-sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002. This paper presents the analysis of results for children <16 years. RESULTS: Children <16 years comprised 449 (5%) of the RBC, 362 (9%) of the FFP and 452 (13%) of the PLT recipients. In children 54% of RBC, 63% FFP and 45% PLT recipients were under 1 year of age and 57% RBC, 60% FFP and 52% PLT were male. Median (IQR) DEduring the study year was 3(2-8); 5(2-13) and 11(6-21) in the RBC, FFP and PLT cohorts, respectively. A total of 20% of RBC, 31% of FFP and 54% of PLT recipients had been exposed to >10 donors. Perinatal conditions were the commonest indication for transfusion in the RBC (36%) and FFP (44%) cohorts and comprised 31% of the PLT cohort. Medical conditions (48%), predominantly malignancy (33%), were the most frequent indication in the PLT cohort. The 10 year (95% CI) survival rates were 81% (77-85%), 72% (67-76%) and 71% (66-75%)for RBC, FFP and PLT cohorts, respectively. CONCLUSIONS: Around half of paediatric transfusion recipients are under 1 year of age. Exposure to components from multiple donors is common. At least 70% of paediatric recipients are long survivors and are at risk for late complications of transfusion.

Size-dependent ecotoxicity of barium titanate particles: the case of Chlorella vulgaris green algae.

Studies have been demonstrating that smaller particles can lead to unexpected and diverse ecotoxicological effects when compared to those caused by the bulk material. In this study, the chemical composition, size and shape, state of dispersion, and surface's charge, area and physicochemistry of micro (BT MP) and nano barium titanate (BT NP) were determined. Green algae Chlorella vulgaris grown in Bold's Basal (BB) medium or Seine River water (SRW) was used as biological indicator to assess their aquatic toxicology. Responses such as growth inhibition, cell viability, superoxide dismutase (SOD) activity, adenosine-5-triphosphate (ATP) content and photosynthetic activity were evaluated. Tetragonal BT (~170 nm, 3.24 m(2) g(-1) surface area) and cubic BT (~60 nm, 16.60 m(2) g(-1)) particles were negative, poorly dispersed, and readily aggregated. BT has a statistically significant effect on C. vulgaris growth since the lower concentration tested (1 ppm), what seems to be mediated by induced oxidative stress caused by the particles (increased SOD activity and decreased photosynthetic efficiency and intracellular ATP content). The toxic effects were more pronounced when the algae was grown in SRW. Size does not seem to be an issue influencing the toxicity in BT particles toxicity since micro- and nano-particles produced significant effects on algae growth.

Evaluation of percutaneous absorption performance for human female sexual steroids into pentravan cream.

There is a lack of studies on Pentravan cream, a widespread transdermal vehicle which is used by compounding pharmacies. The purpose of this study was to evaluate this transdermal vehicle. The permeation performance for progesterone, estradiol, and estriol in formulations containing each of those drugs separately, as well as an association of estradiol + estriol (Biest), was evaluated regarding their compounding process and their potential biological application. An excised female human skin model was used to predict the permeation and the retention of the active compounds in every skin layer in lieu of conventional tape stripping. Progesterone was the drug with the highest permeation (37.02 mcg cm(-2) at the end of the experiment). Estradiol and estriol in Biest had permeations approximately 4-fold lower (9.44 mcg cm(-2) for estradiol-Biest and 14.02 mcg cm(-2) for estriol-Biest), and the profiles of estradiol in Eemuls and in Biest were almost the same (9.46 mcg cm(-2) for Eemuls). All permeations followed pseudo- first order kinetics. For progesterone, using the percentage of permeation by dose, one can infer that a patient using the 1-g emulsion dose released by the pump containing 50 mg of progesterone will have 38.4 mg of progesterone liberated into his bloodstream, gradually and continuously for 48 hours. The results indicate that the vehicle was able to provide percutaneous absorption rates compatible with and higher than clinical treatment needs. Using the same rationale, the Eemuls would deliver practically the entire amount of estradiol load per dose (1.0 mg), approximately 0.5 mg of estradiol per day. As for the Biest, the dosing used would deliver almost 0.5 mg estradiol/day and 2.0 mg estriol/ day. Thus, according to the results, human female sexual hormones incorporated in the oil-in-water vanishing cream base and applied topically are expected to exert their biological activities systemically with good efficacy due to their satisfactory permeation through human skin. However, one must take into account that a high quantity of drug was delivered. Thus, to avoid patient overdose, care has to be taken regarding the quantity of emulsion used.

PET and SPECT imaging of a radiolabeled minigastrin analogue conjugated with DOTA, NOTA, and NODAGA and labeled with (64)Cu, (68)Ga, and (111)In.

Cholecystokinin-2 (CCK-2) receptors, overexpressed in cancer types such as small cell lung cancers (SCLC) and medullary thyroid carcinomas (MTC), may serve as targets for peptide receptor radionuclide imaging. A variety of CCK and gastrin analogues has been developed, but a major drawback is metabolic instability or high kidney uptake. The minigastrin analogue PP-F11 has previously been shown to be a promising peptide for imaging of CCK-2 receptor positive tumors and was therefore further evaluated. The peptide was conjugated with one of the macrocyclic chelators DOTA, NOTA, or NODAGA. The peptide conjugates were then radiolabeled with either (68)Ga, (64)Cu, or (111)In. All (radio)labeled compounds were evaluated in vitro (IC50) and in vivo (biodistribution and PET/CT and SPECT/CT imaging). IC50 values were in the low nanomolar range for all compounds (0.79-1.51 nM). In the biodistribution studies, (68)Ga- and (111)In-labeled peptides showed higher tumor-to-background ratios than the (64)Cu-labeled compounds. All tested radiolabeled compounds clearly visualized the CCK2 receptor positive tumor in PET or SPECT imaging. The chelator did not seem to affect in vivo behavior of the peptide for (111)In- and (68)Ga-labeled peptides. In contrast, the biodistribution of the (64)Cu-labeled peptides showed high uptake in the liver and in other organs, most likely caused by high blood levels, probably due to dissociation of (64)Cu from the chelator and subsequent transchelation to proteins. Based on the present study, (68)Ga-DOTA-PP-F11 might be a promising radiopharmaceutical for PET/CT imaging of CCK2 receptor expressing tumors such as MTC and SCLC. Clinical studies are warranted to investigate the potential of this tracer.

Ecotoxicological studies of micro- and nanosized barium titanate on aquatic photosynthetic microorganisms.

The interaction between live organisms and micro- or nanosized materials has become a current focus in toxicology. As nanosized barium titanate has gained momentum lately in the medical field, the aims of the present work are: (i) to assess BT toxicity and its mechanisms on the aquatic environment, using two photosynthetic organisms (Anabaena flos-aquae, a colonial cyanobacteria, and Euglena gracilis, a flagellated euglenoid); (ii) to study and correlate the physicochemical properties of BT with its toxic profile; (iii) to compare the BT behavior (and Ba(2+) released ions) and the toxic profile in synthetic (Bold's Basal, BB, or Mineral Medium, MM) and natural culture media (Seine River Water, SRW); and (iv) to address whether size (micro, BT MP, or nano, BT NP) is an issue in BT particles toxicity. Responses such as growth inhibition, cell viability, superoxide dismutase (SOD) activity, adenosine-5-triphosphate (ATP) content and photosynthetic efficiency were evaluated. The main conclusions are: (i) BT have statistically significant toxic effects on E. gracilis growth and viability even in small concentrations (1µgmL(-1)), for both media and since the first 24 h; on the contrary of on A. flos-aquae, to whom the effects were noticeable only for the higher concentrations (after 96 h: ≥75 µg mL(-1) for BT NP and =100 µg mL(-1) for BT MP, in BB; and ≥75 µg mL(-1) for both materials in SRW), in spite of the viability being affected in all concentrations; (ii) the BT behaviors in synthetic and natural culture media were slightly different, being the toxic effects more pronounced when grown in SRW - in this case, a worse physiological state of the organisms in SRW can occur and account for the lower resistance, probably linked to a paucity of nutrients or even a synergistic effect with a contaminant from the river; and (iii) the effects seem to be mediated by induced stress without a direct contact in A. flos-aquae and by direct endocytosis in E. gracilis, but in both organisms the contact with both BT MP and BT NP increased SOD activity and decreased photosynthetic efficiency and intracellular ATP content; and (iv) size does not seem to be an issue in BT particles toxicity since micro- and nano-particles produced significant toxic for the model-organisms.

Resistance to the tyrosine kinase inhibitor axitinib is associated with increased glucose metabolism in pancreatic adenocarcinoma.

Alterations in energy (glucose) metabolism are key events in the development and progression of cancer. In pancreatic adenocarcinoma (PDAC) cells, we investigated changes in glucose metabolism induced by resistance to the receptor tyrosine kinase inhibitor (RTKI) axitinib. Here, we show that human cell lines and mouse PDAC cell lines obtained from the spontaneous pancreatic cancer mouse model (Kras(G12D)Pdx1-cre) were sensitive to axitinib. The anti-proliferative effect was due to a G2/M block resulting in loss of 70-75% cell viability in the most sensitive PDAC cell line. However, a surviving sub-population showed a 2- to 3-fold increase in [C-14]deoxyglucose ([C-14]DG) uptake. This was sustained in axitinib-resistant cell lines, which were derived from parental PDAC. In addition to the axitinib-induced increase in [C-14]DG uptake, we observed a translocation of glucose transporter-1 (Glut-1) transporters from cytosolic pools to the cell surface membrane and a 2-fold increase in glycolysis rates measured by the extracellular acidification rate (ECAR). We demonstrated an axitinib-induced increase in phosphorylated Protein Kinase B (pAkt) and by blocking pAkt with a phosphatidylinositol-3 kinase (PI3K) inhibitor we reversed the Glut-1 translocation and restored sensitivity to axitinib treatment. Combination treatment with both axitinib and Akt inhibitor in parental pancreatic cell line resulted in a decrease in cell viability beyond that conferred by single therapy alone. Our study shows that PDAC resistance to axitinib results in increased glucose metabolism mediated by activated Akt. Combining axitinib and an Akt inhibitor may improve treatment in PDAC.

Use of plasma "reconstitution" during cardio pulmonary bypass for a heart transplant after previous left ventricular assist device implant surgery.

The case report describes a novel technique of pre-emptive plasma "reconstitution" prior to disengagement from cardiopulmonary bypass (CPB) to minimize RV volume overload. The concomitant use of hemoconcentration facilitates volume and blood product management in cardiac transplant after previous left ventricular assist device implant surgery.