Bisphosphonates and risk of cancers: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether bisphosphonates are associated with risk of cancers. Therefore, this meta-analysis aimed to evaluate the effect of bisphosphonates on overall cancers. METHODS: A search in Pubmed, Embase, Cochrane Library and Web of Science databases was conducted, from the inception date of each resource to September 26, 2019. The summarised effect estimates with 95% CIs were calculated using a random-effect model. Heterogeneity and publication bias were explored. RESULTS: Thirty-four articles were included in this study (4,508,261 participants; 403,196 cases). The results revealed that bisphosphonates significantly decreased the risk of colorectal cancer (RR = 0.89, 95% CI: 0.81-0.98), breast cancer (RR = 0.87, 95% CI: 0.82-0.93) and endometrial cancer (RR = 0.75, 95% CI: 0.61-0.94), but no significant association was observed in all-cause cancer. Furthermore, nitrogen-containing bisphosphonates only had protective effects both on breast cancer (RR = 0.94, 95% CI: 0.90-0.99) and endometrial cancer (RR = 0.70, 95% CI: 0.54-0.92). Non-nitrogen-containing bisphosphonates tended to increase the risk of liver cancer (RR = 2.14, 95% CI: 1.23-3.72) and pancreas cancer (RR = 1.75, 95% CI: 1.32-2.33). CONCLUSION: Bisphosphonates are significantly associated with risk reduction of colorectal, breast and endometrial cancer, especially nitrogen-containing bisphosphonates. It should be noted that non-nitrogen-containing bisphosphonates might increase the risk of liver and pancreas cancer. Large prospective cohort studies are needed to find the causal association between bisphosphonates and risk of cancers.

Nitrogen-Containing Heterocycles as Anticancer Agents: An Overview.

BACKGROUND: Cancer is spreading all over the world, and it is becoming the leading cause of major deaths. Today's most difficult task for every researcher is to invent a new drug that can treat cancer with minimal side effects. Many factors, including pollution, modern lifestyle and food habits, exposure to oncogenic agents or radiations, enhanced industrialization, etc. can cause cancer. Treatment of cancer is done by various methods that include chemotherapy, radiotherapy, surgery and immunotherapy in combination or singly along with kinase inhibitors. Most of the anti-cancer drugs use the concept of kinase inhibition. OBJECTIVE: The number of drugs being used in chemotherapy has heterocycles as their basic structure in spite of various side effects. Medicinal chemists are focusing on nitrogen-containing heterocyclic compounds like pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, azole, benzimidazole, etc. as the key building blocks to develop active biological compounds. The aim of this study is to attempt to compile a dataset of nitrogen-containing heterocyclic anti-cancer drugs. METHODS: We adopted a structural search on notorious journal publication websites and electronic databases such as Bentham Science, Science Direct, PubMed, Scopus, USFDA, etc. for the collection of peer-reviewed research and review articles for the present review. The quality papers were retrieved, studied, categorized into different sections, analyzed and used for article writing. CONCLUSION: As per FDA databases, nitrogen-based heterocycles in the drug design are almost 60% of unique small-molecule drugs. Some of the nitrogen-containing heterocyclic anti-cancer drugs are Axitinib, Bosutinib, Cediranib, Dasatanib (Sprycel®), Erlotinib (Tarceva®), Gefitinib (Iressa®), Imatinib (Gleevec®), Lapatinib (Tykerb ®), Linifanib, Sorafenib (Nexavar®), Sunitinib (Sutent®), Tivozanib, etc. In the present review, we shall focus on the overview of nitrogen-containing heterocyclic active compounds as anti-cancer agents.

A tumour mRNA-triggered nanoassembly for enhanced fluorescence imaging-guided photodynamic therapy.

A multifunctional theranostic nanoplatform, which integrates diagnostic and therapeutic functions in a single nanosystem, holds great promise for guiding disease treatment and improving the corresponding therapy efficacy. We report the development of a novel g-C3N4 nanosheet-based theranostic nanoassembly for both enhanced imaging of cancer-relevant mRNA in living cells and imaging-guided on-demand photodynamic therapy (PDT) for tumors. The nanoassembly was constructed by using highly fluorescent and water-dispersible g-C3N4 nanosheets which act as nanocarriers, enabling efficient and self-tracking transfection of the DNA hairpin probes. The presence of intracellular mRNA will initiate the DNA hairpin probes, ultimately resulting in an amplified fluorescence signal via hybridization and displacement with mRNA. Moreover, enhanced fluorescence imaging-guided precise PDT for tumors in living cells was also demonstrated, allowing the selective ablation of tumors without any obvious side effects. Therefore, the developed theranostic approach can provide a promising platform for low-abundance biomarker discovery and early treatment of related diseases.

Nontoxic Carbon Quantum Dots/g-C3 N4 for Efficient Photocatalytic Inactivation of Staphylococcus aureus under Visible Light.

The widespread use of antibiotics has caused the rapid emergence of antibiotic-resistant bacterial strains and antibiotic resistance genes in the past few decades. Photocatalytic inactivation, a promising approach for the killing of pathogens, efficiently avoids the problems induced by antimicrobial drugs. However, traditional photocatalysts usually have some disadvantages, such as high costs of raw materials, ultraviolet ray excitation, and potential leaching of toxic metals. Here, a metal-free heterojunction photocatalyst, denoted as CQDs/g-C3 N4 , is synthesized through incorporating carbon quantum dots (CQDs) on graphitic carbon nitride (g-C3 N4 ), which significantly enhances photocatalytic inactivation of Staphylococcus aureus (S. aureus) compared with pure g-C3 N4 in vitro. CQDs/g-C3 N4 causes a rapid increase of intracellular reactive oxygen species levels and destruction of cell membranes under visible light, eventually leading to death of bacteria. The efficacy of CQDs/g-C3 N4 is further examined by a mouse cutaneous infection model of S. aureus. CQDs/g-C3 N4 markedly reduces the bacterial loads and prompts lesion recovery in mice, as compared with g-C3 N4 -treated group. In vivo and in vitro toxicity analyses show that the side effects of CQDs/g-C3 N4 are negligible. Considering the efficient photocatalytic inactivation and nontoxicity of CQDs/g-C3 N4 , this visible-light-driven photocatalyst paves a brand new avenue for the treatment of S. aureus infection.

Therapeutic Potential of N-heterocyclic Analogs as Anti-inflammatory Agents.

BACKGROUND: Various mediators and anti-inflammatory drugs were used since from a long time but it is still a challenge for the medicinal chemists to treat or reduce the symptoms of inflammatory diseases. Most of the clinically used anti-inflammatory drugs such as NSAIDs, Coxibs and GCs are allied with considerable toxicity. OBJECTIVE: The search of novel anti-inflammatory agent is not an ending process. Although the drug treatment has been improved steadily but yet, it is still there is a need to develop more potent therapeutic agents. METHOD: Reported literature survey has been studied to summarize the nitrogen containing moieties which were utilized as potential therapeutic agents. RESULTS: A variety of N-heterocyclic analogs are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal and anti-HIV. However, numerous approaches were used to overcome the toxicity level such as co-administration with suitable agent/substance which provides protection against toxicity as well to synthesise new potent and safe anti-inflammatory drug. CONCLUSION: The present review summarizes the synthetic methodology and therapeutic potential of some N-heterocyclic analogs as potent anti-inflammatory agents.

Bisphosphonate use after estrogen receptor-positive breast cancer and risk of contralateral breast cancer.

BACKGROUND: A growing body of evidence suggests that nitrogenous bisphosphonates may reduce the risk of developing a first breast cancer and may prevent metastases among breast cancer survivors. However, their impact on risk of second primary contralateral breast cancer is uncertain. METHODS: Within a nested case-control study among women diagnosed with a first primary estrogen receptor-positive invasive breast cancer at ages 40-79 years, we assessed the association between post-diagnostic bisphosphonate use and risk of second primary contralateral breast cancer. We used multivariable-adjusted conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) comparing 351 contralateral breast cancer case subjects with 662 control subjects (ie, breast cancer patients not diagnosed with contralateral breast cancer) who were incidence density-matched on county; race/ethnicity; and age at, year of, and stage at first breast cancer diagnosis. We performed sensitivity analyses with respect to bisphosphonate type and confounding by indication. All statistical tests were two-sided. RESULTS: Current use of any nitrogenous bisphosphonate and use specifically of alendronate were both associated with reduced risks of contralateral breast cancer compared with never use (OR = 0.41, 95% CI = 0.20 to 0.84 and OR = 0.39, 95% CI = 0.18 to 0.88, respectively). The risk of contralateral breast cancer further declined with longer durations of bisphosphonate use among current users (P(trend) = .03). Results were similar in analyses restricted to patients with a history of osteoporosis or osteopenia. CONCLUSIONS: Bisphosphonate use was associated with a substantial reduction in risk of contralateral breast cancer. If this finding is confirmed in additional studies, nitrogenous bisphosphonate therapy may be a feasible approach for contralateral breast cancer risk reduction.

Conceptos de nutrición enteral en geriatría (II) / No disponible

No disponible

ESR, electrochemical, molecular modeling and biological evaluation of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones as potential anti-Trypanosoma cruzi agents.

Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action.

Generalized eruptive histiocytosis presenting with warty lesions on face.

Generalized eruptive histiocytosis is a benign proliferative disorder of non-Langerhans cells. It is a very rare disease. The disease presents with soft to firm fleshy papules on face, neck and upper trunk. Biopsy is often needed to make the diagnosis because of its rarity and diverse presentation. There is tendency for the disease to regress spontaneously without treatment. Treatment, if any needed, suffices to topical modalities. We report here a case of generalized eruptive histiocytosis which presented with lesions of dual morphology. This is a very rare disease with diverse presentation being reported first ever in our country.

Compuestos nitrogenados de interés en nutrición clínica / Nitrogenous compounds of interest in clinical nutrition

El término " condicionalmente esencial " (o semiesencial), aplicado inicialmente a los aminoácidos, se utiliza de forma generalizada para otros nutrientes. Un nutriente condicionalmente esencial es un compuesto producido usualmente en cantidades adecuadas por síntesis endógena pero que se requiere de forma exógena bajo determinadas circunstancias. Así, la arginina, la glutamina, la cisteína, la glicina, la prolina y la tirosina son aminoácidos semiesenciales. Entre los derivados de aminoácidos, la carnitina, la colina, y las poliaminas tienen también el carácter de compuestos condicionalmente esenciales. Asimismo, los nucleótidos de la dieta se consideran compuestos semiesenciales debido a que algunos tejidos de rápido crecimiento como el intestino, la médula ósea y los linfocitos utilizan preferentemente bases púricas y pirimidínicas preformadas para la síntesis de ácidos nucleicos. Esta revisión se dedica al estudio de nutrientes condicionalmente esenciales de naturaleza nitrogenada y con interés en nutrición hospitalaria. Entre ellos destacan la arginina, implicada en las funciones endotelial, inmunitaria, gastrointestinal y renal, la reproducción, el desarrollo neonatal, la curación de heridas y la tumorigénesis; la glutamina, necesaria para el mantenimiento de la integridad intestinal y con efectos beneficiosos en estados catabólicos como la sepsis, la infección, el trauma y el cáncer; y los nucleótidos, involucrados en el crecimiento y la diferenciación celular, y con efectos sobre el metabolismo lipídico, la microbiota intestinal y el sistema inmunitario (AU)

The term "conditionally essential" (or semi-essential), initially applied to amino acids, has been generalized to other nutrients. A conditionally essential nutrient is a compound usually produced in adequate amounts by endogenous synthesis but that is exogenously required under certain circumstances. Thus, arginine, glutamine, cysteine, glycine, carnitine, choline, and polyamines are conditionally essential compounds. In addition, dietary nucleotides are considered semi-essential since some rapidly growing tissues such as the gut, bone marrow, and lymphocytes, preferentially use preformed purine and pyrimidine bases for nucleic acid synthesis. This review discusses the study of conditionally essential nitrogenous nutrients of interest in clinical nutrition. Among them we highlight arginine, involved in endothelial, immune, gastrointestinal, and renal functions, in reproduction, neonatal development, wound healing, and tumorigenesis; glutamine, necessary for maintaining bowel integrity, and with beneficial effects on catabolic states such as sepsis, infection, trauma, and cancer; and nucleotides, implicated in cell growth and differentiation, and with various effects on lipid metabolism, intestinal microbiota, and immune system (AU)

Contribution of electrospray mass spectrometry for the characterization, design, and development of nitrido technetium and rhenium heterocomplexes as potential radiopharmaceuticals.

Diagnostic nuclear medicine (NM) is among the imaging procedures (together with X-ray, computerized tomography, magnetic resonance, and echography) the clinicians can routinely adopt to image organs or tissues and related disorders. (99m)Tc-based agents are the radiopharmaceuticals of election in diagnostic NM because of the ideal physical properties of the 99mTc nuclide (t1/2 6.01 hr; Egamma 142 keV), low cost, and easy availability through the commercial 99Mo/99mTc generator, and chemical versatility of the element. In the last two decades the synergistic work of clinics, pharmacologists, and coordination chemists has had a tremendous impact in the development of new 99mTc-based radiopharmaceuticals through the recognition of the structure at the molecular level of the agent utilized. This has been achieved by studying the physico-chemical properties of the long-lived 99gTc (t1/2 2.11 x 10(5) year; Ebeta 292 keV) and third-row congener Re isostructural compounds. Electrospray ionization mass spectrometry (ESI-MS) and collision experiments (MS/MS) represent valuable analytical techniques suitable for the characterization of both technetium and rhenium complexes relevant to NM. Unequivocal structural identification of these bioinorganic compounds, either simple coordination complexes ("essential radiopharmaceuticals") or more sophisticated structures carrying bioactive fragments ("receptor-specific" radiopharmaceuticals), can be realized in combination with multinuclear NMR spectroscopy. MS/MS experiments provide useful information on the different metal-ligand bond strength, and comparison of the fragmentation profiles of isostructural technetium and rhenium compounds give additional details on the role played by the metal in determining preferred decomposition channels. The analysis of these data contribute to design novel synthetic strategies for the obtainment of technetium and rhenium compounds relevant to NM. The chemistry underlying the production of a new class of potential radiopharmaceuticals including a terminal nitrogen bond and a mixed coordination sphere comprising heterodiphosphines and/or dithiocarbamates (DTC) is presented in detail together with the ESI-MS and MS/MS investigations.