Factors affecting influenza uptake among healthcare workers in a chain of primary clinics in Cavite, Marikina, Quezon City and Manila during the COVID-19 pandemic era: A cross sectional study

Background@#Healthcare workers (HCWs) are at most risk of contracting influenza and COVID-19 at their workplace. Despite the well established benefits and strong recommendations for influenza vaccination especially during this COVID-19 pandemic, uptake of this vaccine among HCWs appears to be low and decreasing.@*Objective@#This study aimed to determine the factors that affect the uptake of Influenza vaccine among HCWs in the clinical setting during the COVID-19 pandemic.@*Methods@#A cross-sectional study was conducted using a self-administered questionnaire among physicians and allied staff from a chain of primary care clinics. The questionnaire consisted of multiple choice questions covering baseline demographic data, uptake of Influenza vaccine, factors affecting uptake, awareness and perceptions about vaccination. Sample size was 133, with intent to include all HCWs. Independent T-test and Pearson’s Chi-square test were performed to compare the baseline sociodemographic profiles and perception of influenza. Binary logistic regression was performed to analyze the factors associated with influenza uptake.@*Results@#Among 143 participants, 66 were vaccinated. Occupation (p = 0.009) and having been vaccinated with influenza in the past (p<0.001) were significantly associated with influenza vaccine uptake. Physicians were five times more likely to get vaccinated compared to Pharmacists (p = 0.006). Perceptions regarding influenza show no significant association with the uptake of vaccination.@*Conclusion@#Physicians and nurses were more likely to get vaccinated against influenza during the Covid-19 pandemic. Perceived significant exposure to influenza, with direct patient contact or care and more knowledge regarding influenza may be contributory factors. Vaccination may be included not just in company or institutional policies, but also in national health programs. Awareness campaigns can be instituted. Empathy training may help to constantly remind HCWs that they can expose sick patients to influenza and other communicable diseases.

Senna (Cassia) alata (Linn.) Roxb. leaf decoction as a treatment for tinea imbricata in an indigenous tribe in Southern Philippines.

BACKGROUND: Tinea imbricata, a rare form of tinea corporis caused by Trichophyton concentricum, is endemic to the T'boli tribe in the Southern Philippines. Temporary remissions and limited access to antifungal medications make its treatment a pressing public health concern. Anecdotal reports about the use of Senna alata leaf decoction as treatment exist. OBJECTIVE: To determine the efficacy of community-prepared S alata leaf decoction in the treatment of tinea imbricata. METHODS: Tinea imbricata patients were instructed to apply S alata leaf decoction for 4 weeks (28 ± 3 days). Disease severity, pruritus visual analogue scale scores (VAS) and potassium hydroxide (KOH) mounts of skin scrapings were evaluated before and after treatment. Two assessors evaluated disease severity based on photographs. Cohen's kappa statistics were used to assess diagnostic concordance. Adverse drug events were recorded. RESULTS: Twenty patients were enrolled. After 4 weeks, 95% had decreased pruritus VAS scores, with a mean decreased of 4.05 after treatment (P < .0001). There was a significant difference in disease severity scores before and after treatment (P ≤ .05) with an overall agreement of 'moderate' for both assessors (κ = 0.6, 95% CI [0.33, 0.87]). Forty per cent had negative KOH tests after treatment. None had adverse drug events. CONCLUSION: This is the first study that showed the potential of a community-prepared leaf decoction as a treatment option for tinea imbricata. Larger clinical trials establishing its efficacy, effectiveness and safety profile are recommended to enable its promotion among the indigenous people and health authorities as an accessible and affordable treatment for tinea imbricata.

Gabapentin for uremic pruritus: a systematic review of randomized controlled trials.

Uremic pruritus is one of the most prevalent and bothersome dermatologic symptoms in patients with end-stage renal disease. Some studies suggest a possible neuropathic cause of uremic pruritus. Gabapentin, an anticonvulsant, may control pruritus with neuropathic origin. The objectives of this study were to assess the efficacy of gabapentin in reducing pruritus scores of patients with uremic pruritus and evaluate its safety among dialysis patients. Meta-analysis of randomized controlled trials, using gabapentin as treatment for uremic pruritus among hemodialysis patients was included and analyzed using Review Manager Version 5.1.4 software. Seven out of 17 screened articles were included, with a total of 315 participants. Meta-analysis of the incidence of improved pruritus scores after treatment from four studies (n = 171) showed that treatment with gabapentin decreased the severity of uremic pruritus as compared to the placebo (risk ratio = 0.18; 95% confidence interval: 0.09, 0.33; I2  = 4%: P =< 0.00001). Six studies (n = 290) presented with incidence of adverse drug events such as dizziness, drowsiness, and somnolence. In the pooled analysis, treatment with gabapentin was associated with a higher incidence of adverse drug events compared to the comparator drugs, but the results were not significant (risk ratio = 1.3, 95% confidence interval: 0.81, 2.11; P = 0.28, I2  = 37%). The results of this systematic review suggest that gabapentin is efficacious and safe in improving uremic pruritus among dialysis patients.

Treatment of morphea with narrowband ultraviolet B: A case series

Introduction@#Morphea, is a rare autoimmune disease presenting with fibrotic changes in the dermis and subcutis. It is a benign condition associated with significant atrophy and sclerosis leading to disfigurement, flexure contractures, and impaired function. Ultraviolet A1 and photochemotherapy are highly effective treatment options but are not readily available in the country. Narrowband ultraviolet B (NBUVB), on the other hand, is readily available, affordable, and safe to use. @*Case summary@#Three patients diagnosed with different variants of morphea (bilateral generalize morphea, unilateral generalized morphea, and circumscribed morphea). underwent 30 sessions of NBUVB. Treatment response was assessed using tightness and itch Visual Analogue Scale (VAS), Modified Skin Score (MSS), photographic comparison, ultrasonographic measurement, and histopathologic analysis. NBUVB treatment resulted to 14-60% decrease in the tightness and itch VAS. MSS was also reduced by 35-50%. The size, pigmentation, and erythema of the lesions also decreased. Ultrasonography showed an improvement in the thickness of lesions after treatment. Histopathologic study showed less packed collagen with increase in inter-bundle spaces.@*Conclusion@#Response to treatment was influenced by the age of the lesion and anatomical location. More chronic lesions tend to have less response. Lesions on the face exhibited the greatest improvement while lesions on the lower extremities had the least improvement. This is the first case series study in the country that uses NBUVB as treatment for morphea. The improvement of the sclerotic and atrophic lesions treated with narrowband UVB treatment may be an acceptable substitute for UVA1 and PUVA.

Basal cell nevus syndrome in a 56-year old Filipino female: A case report

Introduction@#Basal cell nevus syndrome (BCNS) (Gorlin-Goltz syndrome or Nevoid basal cell carcinoma syndrome) is a rare inherited multisystem and tumor-predisposing disorder caused by the patched tumor suppressor gene mutations and suppressor of fused gene. Its diagnosis follows a set of criteria based on specific cutaneous features and radiologic findings. Although an autosomal dominant disorder with a high degree of penetrance, BCNS has variable expression making its diagnosis difficult. The limited epidemiologic data among Asians especially in the Philippines hamper early detection or cause frequent misdiagnosis of the condition.@*Case report@#A 56-year-old Filipino female with Fitzpatrick skin type V presented with early onset multiple basal cell carcinomas and bilateral palmoplantar pits. Radiologic investigation reveals odontogenic keratocyst, calcification of the falx cerebri, bridging of the sella turcica, bifid/splayed ribs and vertebral anomalies. The patient exhibits coarse facial features and bilateral cataracts. Cranial computed tomography scan shows cerebrocerebellar atrophy with ventricular dilatation. Management included wide excision of the nodular basal cell carcinomas (BCC), application of 5-flourouracil cream on the superficial BCC and electrodessication and curettage of the smaller lesions. Oral acitretin was also prescribed.@*Conclusion@#This is a case that highlights the approach to diagnosis, clinical features and management of BCNS in a Filipino patient. Since various phenotypic presentations may exist among dark-skinned individuals, early diagnosis poses a challenge among physicians. Epidemiologic and prevalence studies among Filipinos may be done to aid in the diagnosis and early management of this rare genodermatosis.

Binge eating behaviours and food cravings in women with Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS), the most common endocrine condition in women, is often anecdotally associated with binge eating behaviours and food cravings; however there is a paucity of research. This study aimed to report the prevalence of binge eating and food cravings and their relation to obesity risk in women with PCOS. Participants completed an online survey including the Bulimia Investigatory Test, Edinburgh, Food Cravings-Trait Questionnaire and the Three Factor Eating Questionnaire revised-18. The study included obese (n = 340), overweight (n = 70) and lean (n = 45) women with PCOS and lean healthy women (n = 40). Sixty percent of obese women with PCOS were categorised with binge-eating behaviour, with 39% presenting with clinically significant behaviour. Obese women with PCOS presented with high mean food cravings-trait scores (131.6 ± 28.9) that were significantly greater compared with lean (114.0 ± 34.9) and overweight women with PCOS (120.1 ± 29.5; p < 0.001). Multiple regression exploring relations between eating styles and adiposity explained 57% of the variance in binge eating symptom scores in women with PCOS (F = 130.4; p < 0.001, n = 463): significant predictors were food cravings total score (beta = 0.53; p < 0.001), emotional eating score (beta = 0.18; p < 0.001), body mass index (beta = 0.11; p < 0.001) and uncontrolled eating score (beta = 0.009; p = 0.02). Compared with lean healthy women, lean women with PCOS exhibited significantly higher binge eating symptom scores (10.9 ± 7.8 versus 7.4 ± 6.0; p < 0.05), though similar total food craving scores (114.0 ± 34.9 versus 105.6 ± 26.6: NS). This study is the largest, to date, to robustly report that a high proportion of women with PCOS exhibit binge eating behaviours. We recommend screening women with PCOS for binge eating behaviours to help inform the choice of weight management approach for this clinical population.

Pituitary adenylate cyclase-activating polypeptide (PACAP) in the bed nucleus of the stria terminalis (BNST) increases corticosterone in male and female rats.

Single nucleotide polymorphisms (SNP) in the genes for pituitary adenylate cyclase-activating polypeptide (PACAP) and the PAC1 receptor have been associated with several psychiatric disorders whose etiology has been associated with stressor exposure and/or dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In rats, exposure to repeated variate stress has been shown to increase PACAP and its cognate PAC1 receptor expression in the bed nucleus of the stria terminalis (BNST), a brain region implicated in anxiety and depression-related behaviors as well as the regulation of HPA axis activity. We have argued that changes in BNST PACAP signaling may mediate the changes in emotional behavior and dysregulation of the HPA axis associated with anxiety and mood disorders. The current set of studies was designed to determine whether BNST PACAP infusion leads to activation of the HPA axis as determined by increases in plasma corticosterone. We observed an increase in plasma corticosterone levels 30min following BNST PACAP38 infusion in male and female rats, which was independent of estradiol (E2) treatment in females, and we found that plasma corticosterone levels were increased at both 30min and 60min, but returned to baseline levels 4h following the highest dose. PACAP38 infusion into the lateral ventricles immediately above the BNST did not alter plasma corticosterone level, and the increased plasma corticosterone following BNST PACAP was not blocked by BNST corticotropin releasing hormone (CRH) receptor antagonism. These results support others suggesting that BNST PACAP plays a key role in regulating stress responses.

Cocaine- and amphetamine-regulated transcript peptide (CARTp): distribution and function in rat urinary bladder.

We investigated the distribution of CARTp(55-102) in rat lower urinary tract and evaluated its effect on urinary bladder function in vitro. Immunohistochemistry and a vertical isolated tissue bath system were used. Neurons, clusters of nonneuronal endocrine cells, and nerve fibers stained positive for CARTp(55-102) in young adult rat urinary bladder. The CARTp-expressing neuronal elements were nitric oxide synthase (NOS)- and tyrosine hydroxylase (TH)-IR, whereas all nonneuronal CARTp-IR elements stained positively only for TH (100 %). In isolated bladder strips, CARTp significantly increased the amplitude of electric field stimulation (EFS)-induced detrusor contractions at stimulation frequencies ≤12.5 Hz (p ≤ 0.001) as well as amplitude and frequency of spontaneous phasic urinary bladder smooth muscle (UBSM) contractions (p ≤ 0.05). The responses to CARTp stimulation were dose-dependent and increased in the presence of the urothelium. To determine if the CARTp increase in nerve-mediated contractions may involve an action of CARTp on specific neural pathways, we blocked cholinergic, purinergic, and adrenergic pathways and determined CARTp actions on EFS-medicated contractions. CARTp enhancement of EFS-mediated contractions does not involve alteration in purinergic, adrenergic, or cholinergic pathways. The study demonstrates that CARTp(55-102) is highly expressed in rat urinary bladder. CARTp increased the amplitude of EFS-induced detrusor contractions as well as the amplitude and frequency of spontaneous phasic urinary bladder smooth muscle contractions. We conclude that CARTp may alter the release of compounds from the urothelium that leads to an enhancement of UBSM contractility/excitability.

Role of c-Jun N-terminal kinase (JNK) activation in micturition reflexes in cyclophosphamide (CYP)-induced cystitis in female rats.

c-Jun N-terminal kinase (JNK) is member of the mitogen-activated protein kinase (MAPK) family, activated through phosphorylation following cytokine exposure and stress. In this study, phosphorylation of JNK was examined in the urinary bladder with cyclophosphamide (CYP)-induced cystitis and the effects of SP600125, a selective inhibitor of phosphorylation of JNK, on urinary bladder function were assessed using conscious, open outlet, cystometry with continuous instillation of intravesical saline. We induced bladder inflammation in adult female Wistar rats by injecting CYP intraperitoneally to produce acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every third day for 10 days) treatments. Western blotting of urinary bladder demonstrated a significant (p ≤ 0.01) increase (i.e., phosphorylation) in JNK activation with 4- and 48-h CYP-induced cystitis. Immunohistochemistry and image analyses demonstrated a significant (p ≤ 0.01) increase in JNK activation in the urothelium with 4- and 48-h CYP-induced cystitis. Blockade of JNK phosphorylation significantly (p ≤ 0.01) increased bladder capacity and intercontraction void intervals in CYP-treated rats (4 and 48 h). Furthermore, blockade of JNK phosphorylation reduced (p ≤ 0.01) neuropeptide (substance P, calcitonin gene-related peptide) expression in the urinary bladder with CYP-induced cystitis (4 and 48 h). In contrast, blockade of JNK phosphorylation was without effect on bladder function or neuropeptide expression in urinary bladder in control (no inflammation) rats. Blockade of JNK phosphorylation may represent a novel target for improving urinary bladder function with CYP-induced cystitis.

Impaired olfactory bulb neurogenesis depends on the presence of human wild-type alpha-synuclein.

Synucleinopathies including Parkinson's disease (PD) are characterized by the accumulation of alpha-synuclein (α-syn) within neural cell bodies and their processes. Transgenic mice overexpressing human wild-type or mutant forms of α-syn under the control of different promoters were developed to analyse the underlying neuropathology of PD. One of the earliest clinical symptoms associated with PD is olfactory impairment. The generation of new neurons persists up to adulthood in mammals, in particular the olfactory bulb (OB). In order to assess this process in relation to α-syn accumulation, we used mice overexpressing human wild-type α-syn under the regulatable control (tet-off) of the calcium/calmodulin-dependent protein kinase IIα-promoter (CaMKII). We observed a decrease in OB neurogenesis in transgenic animals compared to controls using 5-bromo-2'-deoxyuridine (BrdU) to label newly generated cells (neuron-specific nuclear protein; NeuN). After cessation of transgene expression we detected an increase in newly generated cells both in granular (GCL) and glomerular (GLOM) layers of the OB. This led to a rescue of newly generated neurons (BrdU(+)/NeuN(+)) within the GLOM with a distinct specificity for the dopaminergic subpopulation. In contrast, we did not detect a cell-specific rescue of neuronal cells in the GCL suggesting diverse effects of alpha-synucleinopathy in both interneuronal layers of the OB. Colabelling of BrdU with glial markers showed that a differentiation into neither astroglia nor microglia attributed to the observed phenotype in the GCL. In particular, BrdU(+) particles located within microglial cells were predominantly associated close to the membrane therefore the resembling phagocytosed nuclear fragments of BrdU(+) cells. Thus, our study further contributes insights into α-syn accumulation as a causative player in the impairment of adult neurogenesis and emphasizes its diverse role in cell renewal of distinct OB cell layers.

Antimicrobial applications of electroactive PVK-SWNT nanocomposites.

The antibacterial properties of a nanocomposite containing an electroactive polymer, polyvinyl-N-carbazole (PVK) (97 wt %), and single-walled carbon nanotubes (SWNT) (3 wt %) was investigated as suspensions in water and as thin film coatings. The toxic effects of four different PVK-SWNT (97:3 wt %) nanocomposite concentrations (1, 0.5, 0.05, and 0.01 mg/mL) containing 0.03, 0.015, 0.0015, and 0.0003 mg/mL of SWNT, respectively, were determined for planktonic cells and biofilms of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis). The results showed that the nanocomposite PVK-SWNT had antibacterial activity on planktonic cells and biofilms at all concentration levels. Higher bacterial inactivation (94% for E. coli and 90% for B. subtilis) were achieved in planktonic cells at a PVK-SWNT concentration of 1 mg/mL. Atomic force microscopy (AFM) imaging showed significant reduction of biofilm growth on PVK-SWNT coated surfaces. This study established for the first time that the improved dispersion of SWNTs in aqueous solutions in the presence of PVK enhances the antimicrobial effects of SWNTs at very low concentrations. Furthermore, PVK-SWNT can be used as an effective thin film coating material to resist biofilm formation.

Antimicrobial graphene polymer (PVK-GO) nanocomposite films.

The first report on the fabrication and application of a nanocomposite containing poly-N-vinyl carbazole (PVK) polymer and graphene oxide (GO) as an antimicrobial film was demonstrated. The antimicrobial film was 90% more effective in preventing bacterial colonization relative to the unmodified surface. More importantly, the nanocomposite thin film showed higher bacterial toxicity than pure GO-modified surface.

Transient switch-on/off currents in molecular junctions.

Based on the nonequilibrium density matrix theory we put forward a unified description of the transient and the steady state current formation through a molecular junction. It is demonstrated that the current follows the time evolution of the populations of those molecular charged states which participate in the inter-electrode charge transmission. As an example, the formation of switch-on/switch-off currents is analyzed for a junction where the molecule has two active terminal sites. It is shown that just after a sudden voltage switch-on or switch-off, the resulting transient currents can significantly exceed their steady state value. This feature is caused by molecular charging or discharging processes, which are fast compared to those processes responsible for establishing the steady state current in the junction. The largest transient currents appear if the coupling of the molecule to the adjacent electrodes is asymmetric, or if the applied voltage causes a transformation of extended molecular states into localized ones.

Suppression of neuroblastoma growth by dipeptidyl peptidase IV: relevance of chemokine regulation and caspase activation.

Imbalanced protease expression and activities may contribute to the development of cancers, including neuroblastoma (NB). NB is a fatal childhood cancer of the sympathetic nervous system that frequently overexpresses mitogenic peptides, chemokines and their receptors. Dipeptidyl peptidase IV (DPPIV), a cell surface serine protease, inactivates or degrades some of these bioactive peptides and chemokines, thereby regulating cell proliferation and survival. Our studies show that DPPIV is expressed in normal neural crest-derived structures, including superior cervical and dorsal root ganglion cells, sciatic nerve, and in adrenal glands, but its expression is greatly decreased or lost in cells derived from NB, their malignant counterpart. Restoration of DPPIV expression in NB cells led to their differentiation in association with increased expression of the neural marker MAP2 and decreased expression of chemokines, including stromal-derived factor 1 (SDF1) and its receptor CXCR4. Furthermore, DPPIV promoted apoptosis, and inhibited SDF1-mediated in vitro cell migration and angiogenic potential. These changes were accompanied by caspase activation and decreased levels of phospho-Akt and MMP9 activity, which are downstream effectors of SDF1-CXCR4 signaling. Importantly, DPPIV suppressed the tumorigenic potential of NB cells in a xenotransplantation mouse model. These data support a potential role for DPPIV in inhibiting NB growth and progression.

Work-family characteristics as determinants of sickness absence: a large-scale cohort study of three occupational grades.

This study examined the previously unexplored occupational grade-specific relationships of domestic responsibilities, the age of children, and work-family spillover, with registered sickness absence (>3 days' sick leave episodes, a mean follow-up of 17 months; n = 18,366 municipal employees; 76% women). The results showed that negative spillover from work into family life predicted a heightened rate of sickness absence spells among both women and men in all occupational categories (except upper white-collar men), but especially among blue-collar and lower white-collar employees. Furthermore, among all white-collar employees (except upper white-collar men), having young children (<7 years of age) was predictive of an increased absence rate. Bearing the main responsibility for domestic work did not considerably predict sickness absenteeism in any occupational grade. The authors conclude that some specific work-family characteristics play a role in sickness absence, but their impact on sickness absence partly varies according to gender and occupational grade.

Charge transmission through a molecular wire: the role of terminal sites for the current-voltage behavior.

The current-voltage and the conductance-voltage characteristics are analyzed for a particular type of molecular wire embedded between two electrodes. The wire is characterized by internal molecular units where the lowest occupied molecular orbital (LUMO) levels are positioned much above the Fermi energy of the electrodes, as well as above the LUMO levels of the terminal wire units. The latter act as specific intermediate donor and acceptor sites which in turn control the current formation via the superexchange and sequential electron transfer mechanisms. According to the chosen wire structure, intramolecular multiphonon processes may block the superexchange component of the interelectrode current, resulting in a negative differential resistance of the molecular wire. A pronounced current rectification appears if (i) the superexchange component dominates the electron transfer between the terminal sites and if (ii) the multiphonon suppression of distant superexchange charge hopping events between those sites is nonsymmetric.

A tele-obstetric broadband service including ultrasound, videoconferencing and cardiotocogram. A high cost and a low volume of patients.

We established a tele-obstetric service connecting the Department of Obstetrics and Gynaecology at the Nordland Hospital in Bodø to the delivery unit at the Nordland Hospital in Lofoten. The telemedicine service included a videoconferencing link (3 Mbit/s) for transmission of ultrasound scans and a low-speed data link (telephone modem) for transmission of cardiotocograms (CTGs). One hundred and thirty pregnant women entered the antenatal clinic in Lofoten during the eight-month study period. A total of 140 CTGs were recorded. The tele-ultrasound service was used in five cases (4%). The cases were serious malformation, Down's syndrome, breech presentation, vaginal bleeding during pregnancy and triplets. Analysis showed that the cost of patient travel was NOK 2460 per transfer. The variable cost of videoconferencing was NOK 250 per consultation. However, the total investment costs for the telemedicine service, including the broadband infrastructure, was NOK 1.7 million (Euro 212,000). The telemedicine service was not cost saving at annual workloads below 208. We conclude that the installation has to be used by other medical specialities to make it cost-effective.

Comparing no-touch and tympanic thermometer temperature recordings.

Temperature is a vital sign which can be measured using various types of clinical thermometers. Pulmonary artery temperature is considered the 'gold standard', but this measurement is not usually clinically practical. There is currently no consensus for optimal alternative site or equipment. This research compares 178 simultaneous measurements from 5 clinical areas, using two types of thermometers: tympanic and no-touch temporal. No-touch thermometers were all set to oral equivalent. Tympanic thermometers were adjusted to either oral (n=105) or core (n=73) equivalent. Maximum acceptable difference was identified as 1oC. Two data sets (oral/core; oral/oral) were analysed using Bland-Altman method on Excel programmes, comparing all thermometers and separating oral and core-equivalent tympanics. The two thermometers were found not to be equivalent. As a simple comparison between two thermometers, this research cannot identify which thermometer is more accurate.

What information patients require on graduated compression stockings.

Graduated compression stockings are used prophylactically on a variety of patients within acute hospitals. Anecdotal evidence suggests patients have a limited understanding of this treatment. The aim of this qualitative study was to explore patients' experiences of compression stockings and to ascertain perceptions of their use. Information was gathered using telephone interviews from a sample of 12 adults who had been patients within the past 2 months, and who had worn compression stockings for more than 48 hours. The results showed that patients received little or no information from healthcare staff regarding compression stockings, but that they did have knowledge from other sources, such as long-haul flight advice. This raises issues of informed consent and patient empowerment and highlights the need for both verbal and written information. The information gained informed a patient information leaflet, which was developed in partnership with a patient focus group.

Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone.

Giant cell tumor (GCT) of bone is a unique bone lesion that is characterized by an excessive number of multinucleated osteoclasts. GCT consists of neoplastic stromal cells, multinucleated osteoclasts and their precursors, thus serving as a naturally occurring human disease model for the study of osteoclastogenesis. It still remains unclear how stromal cells of GCT recruit osteoclast precursors. In the present study, we characterized the cellular components of GCT and confirmed the presence of CD14(+)-monocytes/CD68(+)-macrophages and CD34(+)-hematopoetic stem cells that express CXCR4, a specific receptor for SDF-1; SDF-1 gene expression and presence of SDF-1 protein were confirmed by real time RT-PCR, in situ hybridization, and immunohistochemistry in the GCT tissue and cultured cells. SDF-1 was present at 25-50 ng/ml in the conditioned media from the GCT cultures, which is in the range of physiological chemotactic concentration. Migration of osteoclast precursors was 2.5-fold higher in response to GCT conditioned media compared to the control media; and migration was inhibited by an average of 36% with anti-SDF-1 neutralizing antibody or competing recombinant SDF-1. These results suggest that SDF-1 is one of the significant chemoattractant factors involved in the recruitment of hematopoietic osteoclast precursor cells during tumor-induced osteoclastogenesis.