The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion.

Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awareness among health professionals and the lack of official guidelines are responsible for delayed diagnosis in children with HPP. The purpose of the current document is to provide an expert opinion directed at optimizing the diagnostic pathway of pediatric HPP. From April to December 2022, a multidisciplinary working group of 6 experts including two pediatric endocrinologists, a pediatric neurologist, a pediatric odontologist, a clinical geneticist, and a molecular biologist gathered in a series of periodic meetings to discuss the main issues related to the diagnosis of HPP in children and formalize an Expert Opinion statement. The experts agreed on a diagnostic trail that begins with the recognition of specific clinical signs, leading to biochemical analyses of TNSALP activity and vitamin B6 serum concentration. Very important are the neurological and dental manifestation of the disease that should be thoroughly investigated. The evaluation of TNSALP activity must consider sex and age variability and low activity must be persistent. Repeated blood measurements are thus necessary. The molecular analysis is then mandatory to confirm the diagnosis and for genetic counseling.

Recurrence of FSGS after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. RESULTS: Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. CONCLUSIONS: Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

Fatal Yellow Fever in a Kidney Transplant Patient.

A kidney-transplanted patient, unvaccinated against yellow fever (YF), developed high fever, progressed rapidly to hepatic insufficiency and coma, and died 8 days later. Real-time polymarase chain reaction for YF virus collected on the seventh day of symptoms was positive. Autopsy showed disseminated infection and midzonal hepatitis with apoptotic hepatocytes and minimal inflammatory reaction.

Discovery and cross-validation of peripheral blood and renal biopsy gene expression signatures from ethnically diverse kidney transplant populations.

We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.

Hemodialysis and Kidney Transplantation as Predisposing Conditions to Onychomycosis.

BACKGROUND/AIM: Onychomycosis (OM) is one of the commonest superficial fungal infections. Patients undergoing hemodialysis (HD) treatment and kidney transplant recipients (KTR) are considered at risk of contracting fungal infections, but the few published data do not reach the conclusion of whether they are predisposed to OM. This study aimed to determine the prevalence and etiology of OM in these patients and to determine the antifungal susceptibility profile of the isolated fungal species. METHODS: We recruited 149 HD patients, 187 KTR, and a control group comprising 174 patients attending an internal medicine service with other diseases than renal diseases. All patients underwent an examination of all toenails to check for the presence of OM. Antifungal susceptibility tests were performed following the Clinical and Laboratory Standards Institute (CLSI) recommendations. RESULTS: The prevalence rates of OM in HD patients (23.4%) and KTR (23.0%) were significantly higher than those in age- and sex-matched control groups (13.2%). In HD patients, OM was associated with diabetes but not with the duration of dialysis. In KTR, OM was more prevalent in those without diabetes and likely also in those using mycophenolate mofetil or azathioprine but was not associated with the duration of transplantation. Trichophyton rubrum was the most prevalent species (45.9%) followed by T. mentagrophytes (24.5%) and Candida parapsilosis (18.0%). Fluconazole, itraconazole, voriconazole, and terbinafine were all efficient against the isolates of dermatophyte, with terbinafine showing the lowest and fluconazole the highest minimal inhibitory concentrations. All isolates of C. parapsilosis were sensitive to the antifungals according to the CLSI criteria. CONCLUSION: We found a high prevalence of OM in HD and KTR patients and suggest that these conditions should be considered a risk factor of OM. All 4 antifungals evaluated in the study showed good in vitro activity against the etiologic agents.

GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of human malignancies, including prostate cancer. Bombesin (BBN) is a 14 amino acids peptide that selectively binds to GRPR. In this study, we developed two novel Al(18)F-labeled lanthionine-stabilized BBN analogs, designated Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthionine-stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with Al(18)F using the aluminum fluoride strategy. Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN was labeled with Al(18)F with good radiochemical yield and specific activity>30 GBq/µmol for both radiotracers. The logD values measured for Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN were -2.14 ± 0.14 and -2.34 ± 0.15, respectively. In athymic nude PC-3 xenografts, at 120 min post injection (p.i.), the uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in prostate cancer (PC-3) mouse models was 0.82 ± 0.23% ID/g and 1.40 ± 0.81% ID/g, respectively. An excess of unlabeled ɛ-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET (µPET) imaging at 30, 60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with (18)F. Both tracers may have potential for GRPR-positive tumor imaging.

Besides the HLA loci: SNPs and non-HLA gene products as immunoregulatory factors in the onset of psoriatic arthritis subtypes.

Psoriatic arthritis (PsA) is described as a multifactorial autoimmune rheumatic disease although its development is surely linked to some specific HLA genes (especially the HLA-Cw*06:02 allele). To date, its complex immunopathogenetic mechanism is not well clarified. Actually, increasing evidence suggest that qualitative and quantitative interplays between some PsA-susceptibility HLA alleles and other genetic, regulatory and environmental factors, may develop distinct subphenotypes of PsA. We first provide a brief summary of current knowledge about the various PsA conditions. Then, we consider the reasons why further analysis of the clinical course of patients affected by distinct PsA subsets, and who receive different therapeutic treatments, should be carried out in conjunction with deeper investigations about the identification of key genes and immunoregulatory agents by applying the most recent advances in biotechnology. This approach could better explain the molecular mechanisms responsible for both the onset and progression of this multi-faceted pathology with the purpose of significantly improving the management of PsA patients.

Preclinical evaluation of a novel ¹¹¹In-labeled bombesin homodimer for improved imaging of GRPR-positive prostate cancer.

Rational-designed multimerization of targeting ligands can be used to improve kinetic and thermodynamic properties. Multimeric targeting ligands may be produced by tethering multiple identical or two or more monomeric ligands of different binding specificities. Consequently, multimeric ligands may simultaneously bind to multiple receptor molecules. Previously, multimerization has been successfully applied on radiolabeled RGD peptides, which resulted in an improved tumor targeting activity in animal models. Multimerization of peptide-based ligands may improve the binding characteristics by increasing local ligand concentration and by improving dissociation kinetics. Here, we present a preclinical study on a novel radiolabeled bombesin (BN) homodimer, designated (111)In-DOTA-[(Aca-BN(7-14)]2, that was designed for enhanced targeting of gastrin-releasing peptide receptor (GRPR)-positive prostate cancer cells. A BN homodimer was conjugated with DOTA-NHS and labeled with (111)In. After HPLC purification, the GRPR targeting ability of (111)In-DOTA-[Aca-BN(7-14)]2 was assessed by microSPECT imaging in SCID mice xenografted with the human prostate cancer cell line PC-3. (111)In labeling of DOTA-[(Aca-BN(7-14)]2 was achieved within 30 min at 85 °C with a labeling yield of >40%. High radiochemical purity (>95%) was achieved by HPLC purification. (111)InDOTA-[Aca-BN(7-14)]2 specifically bound to GRPR-positive PC-3 prostate cancer cells with favorable binding characteristics because uptake of 111In-DOTA-[Aca-BN(7-14)]2 in GRPR-positive PC-3 cells increased over time. A maximum peak with 30% radioactivity was observed after 2 h of incubation. The log D value was -1.8 ± 0.1. (111)In-DOTA-[Aca-BN(7-14)]2 was stable in vitro both in PBS and human serum for at least 4 days. In vivo biodistribution analysis and microSPECT/CT scans performed after 1, 4, and 24 h of injection showed favorable binding characteristics and tumor-to-normal tissue ratios. This study identifies (111)In-DOTA-[(Aca-BN(7-14)]2 as a promising radiotracer for nuclear imaging of GRPR in prostate cancer.

Anthraquinone profile, antioxidant and antimicrobial activity of bark extracts of Rhamnus alaternus, R. fallax, R. intermedia and R. pumila.

The quantity of phenols, as well as antioxidant and antimicrobial activities, were investigated in bark of Rhamnus alaternus L., R. fallax Boiss., R. intermedia Steud. et Hochst., and R. pumila Turra from natural stands in Croatia. The most abundant anthraquinones in the investigated extracts were chrysophanol in R. alaternus (3.14 mg/g), emodin in R. pumila (0.339 mg/g), and physcion in R. fallax (2.70 mg/g) and R. intermedia (0.285 mg/g). The species exhibiting the highest antioxidant activity were R. fallax and R. pumila. A positive correlation was observed between total phenolic and flavonoid levels of the extracts and antioxidant activity in some of the assays. All species showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Aspergillus niger and Microsporum gypseum with minimal inhibitory concentrations equal to or below 2.500 mg/mL. The results indicate that the investigated Rhamnus species are a source of anthraquinones and other phenols, which act as multifunctional antioxidants with antimicrobial activity.

Immunogenetics and HPLC analyses contribute to understanding the etiopathology of rheumatoid arthritis through studies on ancient human remains.

Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying origins and the etiopathology of diseases, especially those having an autoimmune background such as rheumatoid arthritis (RA). We wish to demonstrate how reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to immunogenetic screening, even involving analytical chemistry. Here, we focused our investigation on the skeleton of Cardinal Carlo de'Medici (1595-1666) for whom RA and psoriatic arthritis (PsA) were postulated after paleopathologic examination. RA susceptibility is linked to specific HLA alleles belonging to DRB1 04 locus, such as DRB1 0401, while Cw 0602 and DRB1 07 predispose to PsA. Thus, we genotyped the Cardinal?s remains to search for RA or PsA risk genes. Ancient DNA is often subjected to hydrolysis followed by fragmentation. For this reason, all immunogenetic tests were preceded by an original RP-HPLC-FL method able to inform on the ancient DNA preservation and the extent of contamination, with the purpose of avoiding the risk of false positive results. After DNA isolation from a piece of bone from the Cardinal, PCR-SSP and reverse-SSO hybridization assays were applied to perform genomic HLA-typing. RP-HPLC-FL analysis revealed a good preservation of DNA without contamination by exogenous genomes. Molecular tests assigned to the Cardinal the genotype DRB1 0401/1102 for HLA-DRB locus and Cw 04/ 12 for HLA-C locus, data that support a genetic predisposition for RA but not for PsA. This multidisciplinary study has allowed us: (i) to ascertain that the remains undoubtedly belonged to the specific subject, Cardinal Carlo de?Medici; (ii) to sustain that the subject suffered from RA rather then that PsA, and (iii) to state that RA was already widespread in Europe at the Renaissance age, despite some authors claiming that the disease was introduced to the Old Continent from America after colonization during the 18th century.

Quantification of 4'-geranyloxyferulic acid, a new natural colon cancer chemopreventive agent, by HPLC-DAD in grapefruit skin extract.

Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy-compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been consider for years merely as biosynthetic intermediates of the most abundant C-prenylated derivatives. Many of the isolated oxyprenylated natural products were shown to exert in vitro and in vivo remarkable anti-cancer and anti-inflammatory effects. 4'-Geranyloxyferulic acid [3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic] has been discovered as a valuable chemopreventive agent of several types of cancer. After development of a high yield and "eco-friendly" synthetic scheme of this secondary metabolite, starting from cheap and non-toxic reagents and substrates, we developed a new HPLC-DAD method for its quantification in grapefruit skin extract. A preliminary study on C18 column showed the separation between GOFA and boropinic acid (having the same core but with an isopentenyloxy side chain), used as internal standard. The tested column were thermostated at 28+/-1 degrees C and the separation was achieved in gradient condition at a flow rate of 1 mL/min with a starting mobile phase of H(2)O:methanol (40:60, v/v, 1% formic acid). The limit of detection (LOD, S/N=3) was 0.5 microg/mL and the limit of quantification (LOQ, S/N=10) was 1 microg/mL. Matrix-matched standard curves showed linearity up to 75 microg/mL. In the analytical range the precision (RSD%) values were

Comparison of three different extraction methods and HPLC determination of the anthraquinones aloe-emodine, emodine, rheine, chrysophanol and physcione in the bark of Rhamnus alpinus L. (Rhamnaceae).

INTRODUCTION: Rhamnus alpinus L. (Rhamnaceae), a traditional plants in the flora of the Abruzzo region, is known to contain active anthraquinone secondary metabolites. However, the content of anthraquinones varies among R. alpinus samples depending on collection season and site. Thus, using simple, reliable and accurate analytical methods for the determination of anthraquinones in R. alpinus extracts allows comparative study of different methods of extraction. OBJECTIVE: After a partial validation of an HPLC method for the simultaneous determination of five anthraquinones, aloe-emodine, rheine, emodine, chrysophanol and physcione, in the bark of R. alpinus, we compared three different methods of extraction. METHODOLOGY: Anthraquinones were extracted from the bark of R. alpinus using different techniques (methanol maceration, ultrasonic and supercritical CO(2) extraction). Separation and quantification of anthraquinones were accomplished using a reversed-phase C(18) column with the mobile phase of H(2)O-methanol (40 : 60, v/v, 1% formic acid) at a wavelength of 254 nm. The qualitative analyses were also achieved at wavelength of 435 nm. RESULTS: All calibration curves were linear over the concentration range tested (10-200 mM) with the determination coefficients >or=0.991. The detection limits (S/N = 3) were 5 mM for each analytes. All five anthraquinones were found in the samples tested at concentrations reported in experimental data. CONCLUSION: The described HPLC method and optimised extraction procedure are simple, accurate and selective for separation and quantification of anthraquinones in the bark of R. alpinus and allow evaluation of the best extraction procedure between the tested assays.

NT-proBNP changes, oxidative stress, and energy status of hypertrophic myocardium following ischemia/reperfusion injury.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive functional marker in heart disease, including left ventricular hypertrophy (LVH) secondary to valvular aortic stenosis (AS). We evaluated the association between NT-proBNP changes, oxidative stress, energy status and severity of LVH in patients with AS. Ten patients undergoing aortic valve replacement for AS were studied. Plasma NT-proBNP concentrations were performed by electroluminescence immunoassay 15min after the induction of anesthesia (t0), before aortic cross-clamping (t1), before clamp removal (t2), 15min after myocardial reperfusion (t3), and 24h after surgery (t4). Heart biopsies were obtained and high energy phosphates (ATP, ADP, AMP) were analyzed by capillary electrophoresis (CE). In plasma samples from the coronary sinus, nitrate plus nitrite (NOx) concentrations were also analyzed by CE. Echocardiographic measurements were acquired and correlations between biochemical markers and severity of AS were assessed. NT-proBNP peaked significantly at t4 (p<0.001). A linear correlation between NT-proBNP values measured at t0 and t4 was found (R(2)=0.89; p<0.001). A negative correlation between NT-proBNP production and phosphorylation potential (ATP/ADP ratio) was observed (R(2)=0.62; p<0.01). NOx values positively correlated with NT-proBNP levels (p<0.01). NT-proBNP inversely correlated with aortic valvular area (r=81, p<0.01), positively correlated with mean (r=0.82, p<0.01) and maximum left ventricle-to-aortic gradients (r=0.80, p<0.01), and with left ventricular mass (r=0.69, p<0.01). NT-proBNP is a useful marker of LVH and severity of AS. It may complement echocardiographic evaluation of patients with AS in identifying the optimum time for surgery.

Italian Stroke Guidelines (SPREAD): evidence and clinical practice.

Evidence-based medicine's aims are to retrieve, screen and compound the best external evidence with the experience of the physician, and to best respond to the specific medical need of each individual patient. Clinical questions are better answered when good systematic reviews of randomised trials or good randomised clinical trials are available. On the other hand, in a clinical scenario, difficulties in applying the evidence may be amplified due to variability of disease conditions, feasibility of intervention and patient's preferences. Guidelines are recommendations, based as much as possible on evidence, aimed at supporting clinical judgement/diagnostic skills/treatment decisions in everyday practice. Guidelines may improve the quality of care received by the patient and may contribute towards better consistency of care in a definite geographical area. However, guidelines risk reducing physician skills to critically appraising the evidence. In a clinical scenario, guidelines do not always provide substantial help, especially when no conclusive evidence supports them. The Italian Stroke Guidelines (SPREAD) have contributed towards more evidence-based and better harmonised stroke care in Italy. However, the number of high grade recommendations in SPREAD is still limited. Professionals should not forget that clinical decisions often reflect several issues, not only scientific ones, including personal experience, applicability of intervention and patient's preferences.

Corpus callosum atrophy is associated with gait disorders in patients with leukoaraiosis.

Cognitive impairment and gait disturbances are the most frequent clinical findings in patients with leukoaraiosis (LA). Corpus callosum (CC) atrophy has been associated with dementia in patients with LA, as well as with gait disturbances in patients with normal pressure hydrocephalus. We investigated, in patients with LA, the possible association between gait impairment and CC atrophy, taking into account cognitive deficits and the other brain lesions commonly present in these patients. Thirty patients (M:F=21:9; mean age 72.5+/-6.3 years) with gait disturbances and brain CT images consistent with LA underwent an assessment of gait and a cognitive assessment of global and selective functions. Magnetic resonance imaging (MRI) was used to measure thickness and area of the CC, total LA volume, lacunar infarcts and size of lateral ventricles. We examined the effect of every MRI change on each performance measure. Reduction of CC thickness, particularly that of the anterior segment, had a significant effect on severity of gait impairment, as measured using the gait scale's score. It was independent of any other brain changes revealed by MRI, including LA. An independent, significant association was also found between CC area and the Left Hand Praxis test results. In patients with LA, CC atrophy is associated with gait impairment independently of LA and other brain abnormalities usually present in these patients.

Determination of hydrochlorothiazide and irbesartan in pharmaceuticals by fourth-order UV derivative spectrophotometry.

The fourth-order derivative spectrum from the alcoholic sample is used. HCT can be determined by a specific peak-trough, of low intensity, at 330-340 nm. For IST evaluation, a peak-trough around 250-310 nm is available, common to both products, whose amplitude increases linearly only for low concentration values, while it decreases at higher values. The most difficult aspect of the analysis lies in how to find the optimal concentration range, so that both signals can be evaluated simultaneously. The best results were achieved by using a linear regression for HCT and a regression plane for IST.

HPLC investigated physicochemical compatibility between Artrosilene injectable solution and other pharmaceutical products frequently used for combined therapy into elastomeric Baxter LV5 infusion devices.

Ketoprofen lysine salt(Artrosilene injectable solution) is a non-steroidal anti-inflammatory agent frequently administered by slow intravenous infusion with portable elastomeric infusion systems in association regimen with other analgesic drugs. The aim of this study was to investigate the physicochemical compatibility between ketoprofen lysine salt(Artrosilene injectable solution) and other injectable drugs frequently used in association, such as tramadol hydrochloride, keterolac tromethamine and morphine hydrochloride, into the Infusor LV5, Baxter elastomeric infusion system. Physicochemical properties of drug mixture, including colour, clarity, pH and drug content were observed or measured by a reversed-phase HPLC method with UV detection, before and after (up to 7 days) mixing at room temperature and under light protection. The results obtained demonstrated the physicochemical compatibility of ketoprofen lysine salt(Artrosilene injectable solution) with all drug formulations at every tested mixing ratios into Baxer Infusor LV5 infusion devices.

Physicochemical compatibility between ketoprofen lysine salt injections (OKi Fiale, PG060) and pharmaceutical products frequently used for combined therapy.

Ketoprofen lysine salt (Oki Fiale, PG060) is a non steroidal anti-inflammatory agent frequently administered by intramuscular route in association regimen with other drugs, such as steroidal anti-inflammatory, muscle relaxant, local anaesthetic and anti-spastic drugs or vitamins. The aim of this study was to investigate the physicochemical compatibility between ketoprofen lysine salt (Oki Fiale, PG060) and other injectable drugs frequently used in association. Physicochemical properties of ketoprofen lysine salt mixtures with different drugs, including colour, clarity, pH and drug content were observed or measured before and after (up to 3 hours) mixing at room temperature and under light protection. Results show that the association of Oki Fiale (PG060) with different drugs does not cause, up to three hours from mixing, any significant variation in the physicochemical parameters mentioned above. In conclusion, the results obtained demonstrated the physicochemical compatibility of Ketoprofen lysine salt (Oki Fiale, PG060) with several injectable drugs, except for Spasmex fiale (chemical incompatibility) and Xylocaina Astra 2% iniettabile mixed whit a volume ratio of 2/1 (physical incompatibility).