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Confirming our professional identity in the eyes of the general public: why our language and stories are so important
Elizabeth Matters FACN
In January, a short article from the BBC passed through my newsfeed entitled Nurses: The way the profession is changing. In this article, a collaboration with the Royal College of Nursing, three nurses were showcased who were acting as largely autonomous, advanced practitioners in their clinical areas (Therrien, 2018). I admired the work that these nurses were doing but I did wonder myself if the initiatives were really so new? Or was this was one of the few times the mainstream media had picked up and promoted what advanced practice nurses really do?
As insiders, we are naturally aware of our own work and the work of many colleagues in developing nursing theories, nursing research and specialist knowledge in unique advanced practice areas. Each area demands a huge amount of nursing experience and theoretical knowledge in order to provide unique nursing based solutions. The problem is that we tend to forget to tell the general public and this lack of recognition causes problems when we have to stand our professional ground.
Just to test, non-scientifically, how the general public views the nursing profession, I conducted a very informal survey on my Facebook page where I asked my contacts if they had ever benefited from the specialist knowledge of a talented nurse. I was really hoping to hear some concrete examples where nurses had perhaps shown a person how to care for a medical device, provided ongoing counselling in a chronic disease situation or healed a wound which had been a long-term problem. Unfortunately I was largely disappointed. My respondents all enthusiastically praised nurses as lovely people, but when asked what the nurse had done the same responses came up: 'they were nice', 'they were sensible", 'they reassured me that everything would be fine', 'they held my hand', 'they bought me a snuggly warm blanket.' I know the significance of these things for patients and I am not disputing their importance for a minute but it saddened me that, even with prompting, no-one could pinpoint an example where they had appreciated a nurse's expert knowledge. Eventually, it came out that the nurses had shown skill in patient education, in managing chronic disease processes holistically and in observation and identification of impending problems. Yet, without my persistent questioning, no one would have mentioned these highly important skills. The gratitude to nurses was certainly there but there was little appreciation for nursing as a professional skill.
When one examines the definition of a profession, it is clear that contemporary Australian nursing can fulfil the criteria. We are clearly differentiated in law from other professions and operate within a legal framework which allows us self-regulation. We prepare would-be nurses with an intellectual basis for their practice through higher education. We have a clearly developed code of ethics which protects the public and our patients. We generate a positive effect on our communities through altruism and worthwhile knowledge. Increasingly, we have gained more political power (another criterion for an independent profession) through ACN and ANF activities and through an increased profile in health care policy via roles such as the Chief Nursing and Midwifery Officer (Saks 2012; ten Hoeve, Jansen & Roodbol, 2014). There are many countries with health systems as sophisticated as ours where nurses find it much more difficult to establish their professional credentials, their identity and their minimum expectations for workload and remuneration. Therefore all these achievements in Australian nursing are significant and must be celebrated!
I do believe, however, that each of us can assert more ownership of our unique body of professional knowledge and expertise (Saks 2012). I believe for the future of our profession, it is essential that we do so. If we do not, the general public will continue to have a very vague idea of what we really do and we will continue to have a sense that we have to battle for professional recognition. The public is not confronted with images, stories or language often enough which clearly articulate the nursing knowledge base. We have all seen the media campaigns for nursing recruitment… nurses are depicted smiling, holding people's hands, cuddling babies, holding clipboards, walking down corridors and perhaps passing things to surgeons. In many campaigns where nurses are asked about their job, they emphasise 'caring', 'following a family tradition', 'making a difference', 'doing something good' and 'enjoying gratitude'. There is very rarely any discussion of their knowledge, their specialised skills and what only they can offer to the public.
But if we value caring and so do our patients, isn't that enough for us? Well, unfortunately, it seems it is not. We want more than to be admired as nice people. We want to be respected and recompensed for our knowledge, our years of experience and training and the critical importance of our work to the health care system. That means we have to value our own expertise and not be shy about informing the general public about what that is. We need to depict the complexity of the work we do every day and not downplay it. It is our choice whether we say 'I take people to the toilet all day' or whether we explain our promotion of patient wellbeing through the assessment and facilitation of mobility, skin integrity, fluid balance and elimination.
This change in language may sound like mere wordplay but it is so very important. Our own language speaks volumes about the way we respect our work. If we play down what we do, why should anyone outside the profession bother to promote the great work that lies underneath our self-deprecation on our behalf? Every industry promotes its services and knowledge in a bid for respect, influence and remuneration. Why shouldn't nursing follow suit? We need to be unembarrassed about publicising our pursuit of knowledge, and the development of our own concepts and theories. We need to stop resenting the research-practice divide within our profession and see that research informs our practice and gives us the unique professional knowledge which we need. Conversely, we need to encourage more clinical nurses not to fear research conventions and to assist them to substantiate their 'nursing instinct' about one thing or another with actual rigorous evidence. We need to discuss and define where our expertise lies and then tell the world, diluting the stories we share at home and with our friends about body product catastrophes, unfair workloads and frustration with our medical colleagues. Instead we need to saturate the public consciousness with positive, proud stories of our unique achievements, targets and projects.
It was heartening to see that the BBC, one of the world's biggest news providers, was prepared to celebrate autonomous nursing practice but there is a lot more to do in our own communities. Whether it is right or not, the modern world celebrates and values 'Winners': people and professional groups who are skilled, fast-paced, successful and confident. If we want to feel we are truly respected and valued in society, we have to showcase our expert services as valuable, unique offers and, in so doing, demand nothing but the highest respect.
Saks, M. (2012). 'Defining a profession: the role of knowledge and expertise.' Professions and Professionalism, 2(1):1-10.
Ten Hoeve, Y., Jansen, G. & Roodbol, P. (2014). 'The nursing profession: public image, self-concept and professional identity: a discussion paper', JAN, 70(2):295-309.
Therrien, A. (2018). 'Nursing: the way the profession is changing', BBC News. Available at: www.bbc.com/news/health-42692508.


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In the European Union, more than 1,300 chemicals are banned or restricted for cosmetic use, but here in the states, only 11 fall into that category. However, clean beauty brands aren't buying it. Instead, they are drafting their own rules, formulating without the laundry list of ingredients they believe to be potentially harmful to humans, animals and/or the planet. Further muddying the water is the fact that "The Federal Food, Drug and Cosmetic Act of 1938 does not require the FDA to review cosmetics and their ingredients, with the exception of color additives because many of them are also used in foods and drinks," says Sarah Biggers-Stewart, founder and CEO of Clove + Hallow. So, what actually makes a product clean?
Most brands count safety, sustainability, sourcing and ethics as key pillars, in addition to total ingredient transparency. Generally topping the list of "nasties" are chemicals that have been scientifically linked to health issues: potential carcinogens (they have the ability to cause cancer) reproductive toxins (they can cause adverse effects on sexual function and fertility) and endocrine disruptors (they can negatively interfere with our hormones). There's also the environmental component: Clean brands prioritize ingredients that help the earth, rather than those that flood our landfills or hurt our wildlife.
5 Controversial Makeup Ingredients
Used as preservatives in makeup to prevent the growth of harmful bacteria as they sit on store shelves, parabens are perhaps the most notorious nasties, and have been since 2004 when a scientific article linked them to breast tumors. "Parabens—look for methylparaben, propylparaben, butylparaben and ethylparaben on labels—are effective preservatives," says cosmetic chemist Ginger King, "but there have been studies linking traces of parabens to breast cancer, thus people are avoiding them."
To err on the side of caution, most beauty brands have removed parabens from their products—even reformulating entire lines without them to appease concerned users— and replaced them with natural preservatives like dehydroacetic acid and benzyl alcohol.
Our Clean Pick:
RMS Beauty Living Luminizer Glow Quad Mini ($25)
Carbon Black
When it comes to eyeliner and mascara, many of us would say the darker the better. But what gives many of these jet-black formulas their deep, inky hue is a pigment enhancer called carbon black—it's also listed as Black 2 on some products. Made from coal tar, carbon black is found in nearly all dark liquid eyeliners and many mascaras, and has been deemed "possibly carcinogenic to humans" by the International Agency for Research on Cancer. Merrady Wickes, beauty director at The Detox Market, says the store doesn't carry any products that contain the ingredient.
"It's not only been linked to cancer, but also lung disease and reproductive toxicity," says Marla Beck, founder of Lune+ Aster Cosmetics. "I wanted to add a black liquid eyeliner to our collection, but refused to make one with carbon black. To ensure the same intense color payoff without using it, we formulated with plant pigments. It was in the works for a long time, but we were able to achieve a bold look and long-lasting power, with no negative health effects."
Our Clean Pick:
Lune+Aster Dawn to Dusk Liquid Eyeliner ($24)
Take a look at the ingredient list on a powder blush, bronzer or eye shadow, and you'll probably see talc, a naturally occurring mineral that has been used in makeup for centuries for its smoothing properties. But, according to the FDA, although talc itself is not a carcinogen, it runs the risk of being contaminated with cancer-causing asbestos due to the proximity of asbestos to talc deposits in certain mines around the world. In 2019, the FDA surveyed 50 cosmetics containing talc and confirmed the presence of asbestos in several of them, which were voluntarily recalled by the companies.
Biggers-Stewart says, "While I think the formulation of beauty products with talc can be done safely with proper testing of raw materials for asbestos, we haven't felt the need to use it because there are some really great alternatives out there, such as kaolin clay, arrowroot powder and silica."
Our Clean Pick:
Clove + Hallow Pressed Mineral Foundation ($24)
FD&C Pigments
Primarily used in makeup to create bright, bold shades—Wickes says they can add vibrancy that mineral colors can't (but that's quickly changing)—Food, Drug and Cosmetic (FD&C) pigments derived from coal tar are considered carcinogenic by many brands. Some experts and retailers, however, view the color additives as an inflated threat and do not explicitly ban them, but agree that working with reputable vendors and conducting thorough safety testing on products is key to avoiding any issues.
Kristine Keheley and Krysia Boinis, founders of Vapour Beauty, believe "coal tar–derived FD&C colorants have been linked to cancer for decades and do not belong on your skin, period." As a result, Keheley has figured out a way to disperse mineral pigments and carmine in plant oils in the correct ratios, which allows them to achieve luxurious color payoff. "When switching to clean makeup, lip products are an obvious place to start because, like it or not, we do ingest lip gloss and lipstick every time we wear it," says Boinis. Some experts even estimate that lipstick devotees could consume up to seven pounds of it over the course of their lifetimes.
Our Clean Pick:
Vapour Beauty High Voltage Lipstick ($35)
Synthetic Fragrance
"There are hundreds of red-flag ingredients I avoid, but one of my top three is synthetic fragrance," says Biggers-Stewart, noting that it is found in many lip glosses, setting sprays and foundations, and is usually a subtle fruity or cupcake-like scent. "My main gripe is that it's treated as a trade secret, meaning the 15-plus compounds a scent comprises do not have to be disclosed, which blurs the line of informed consent in my opinion."
Another common gripe is that synthetic fragrances often contain phthalates, which are known endocrine disruptors, and that makeup doesn't need fragrance to function. Keheley adds, "If I see 'fragrance' in the ingredient list without any additional information or indication that it's naturally derived, I avoid it."
Our Clean Pick:
Kjaer Weis Lip Gloss ($38)

subset: commoncrawl


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New post from Sean Redmond
Greetings Patrol Volunteers
Greetings Patrol Volunteers,
After five and half years as Executive Director of Stonewall Citizens' Patrol, I have made the difficult decision to transition out of the organization effective December 31st. Without reservation, I have genuinely cherished my time serving as your Executive Director, volunteering on patrols, and working with the Board of Directors. The opportunity to be inspired and motivated, at every turn, by the Stonewall Citizens' Patrol family is truly transformative for all of us and our community. I know that the organization will continue to do phenomenal work on behalf of community safety and our community.
Stonewall Citizens' patrol has a stellar group of community leaders and volunteers that will continue the organization's mission, vision, and core values. With great enthusiasm, a strong work ethic, and many years of community experience, the Board of Directors and organizational leaders will maintain its programmatic and financial strength during this transition.
My tenure at Stonewall Citizens' Patrol has been an incredible experience. I have had the opportunity to witness the positive impact the organization has on the communities we serve.
As I transition into a new role of serving veterans and families in San Diego County, I will always be thankful for the support of our Board, donors, and volunteers for helping make Stonewall Citizens' Patrol a strong organization that has become a vital community safety resource for the lives of so many in our community.
I look forward to celebrating all Stonewall Citizens' Patrol future successes together!
Sean Redmond


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- Research article
- Open access
- Published:
Living with an imperfect cell wall: compensation of femAB inactivation in Staphylococcus aureus
BMC Genomics volume 8, Article number: 307 (2007)
9147 Accesses
28 Citations
Synthesis of the Staphylococcus aureus peptidoglycan pentaglycine interpeptide bridge is catalyzed by the nonribosomal peptidyl transferases FemX, FemA and FemB. Inactivation of the femAB operon reduces the interpeptide to a monoglycine, leading to a poorly crosslinked peptidoglycan. femAB mutants show a reduced growth rate and are hypersusceptible to virtually all antibiotics, including methicillin, making FemAB a potential target to restore β-lactam susceptibility in methicillin-resistant S. aureus (MRSA). Cis-complementation with wild type femAB only restores synthesis of the pentaglycine interpeptide and methicillin resistance, but the growth rate remains low. This study characterizes the adaptations that ensured survival of the cells after femAB inactivation.
In addition to slow growth, the cis-complemented femAB mutant showed temperature sensitivity and a higher methicillin resistance than the wild type. Transcriptional profiling paired with reporter metabolite analysis revealed multiple changes in the global transcriptome. A number of transporters for sugars, glycerol, and glycine betaine, some of which could serve as osmoprotectants, were upregulated. Striking differences were found in the transcription of several genes involved in nitrogen metabolism and the arginine-deiminase pathway, an alternative for ATP production. In addition, microarray data indicated enhanced expression of virulence factors that correlated with premature expression of the global regulators sae, sarA, and agr.
Survival under conditions preventing normal cell wall formation triggered complex adaptations that incurred a fitness cost, showing the remarkable flexibility of S. aureus to circumvent cell wall damage. Potential FemAB inhibitors would have to be used in combination with other antibiotics to prevent selection of resistant survivors.
The peptidoglycan structure of Staphylococcus aureus is a dynamic, three-dimensional meshwork consisting of multiple layers of glycan strands that are crosslinked through peptide bridges. It determines the bacterial shape and confers protection against the high internal turgor. Characteristic for the staphylococcal peptidoglycan is the long and flexible pentaglycine interpeptide, which branches off the ε-amino group of the L-lysine of the peptidoglycan stem peptide. The pentaglycine interpeptide is synthesized in a sequential fashion by the FemABX family of nonribosomal peptidyl transferases, which use glycyl-tRNA as a glycine donor. While FemX (synonym: FmhB) adds the first glycine, FemA and FemB add Gly2,3 and Gly4,5, respectively [1–4]. Although structurally and functionally related, these factors cannot substitute for one another [5]. Growth of mutants with a shortened interpeptide is strongly impaired [2]. They display a massive reduction in cell wall crosslinking, aberrant septum formation, and hypersusceptibility to antibiotics including all β-lactams [1, 2]. In methicillin-resistant S. aureus (MRSA), methicillin resistance is completely abolished upon inactivation of femA, suggesting that the monoglycine peptidoglycan is a very poor substrate for the native penicillin-binding proteins (PBPs) as well as for the low affinity PBP2a encoded by mecA, which confers resistance to β-lactams. FemX and/or FemA were therefore regarded as potential targets for novel antibacterial agents, which could restore β-lactam susceptibility in MRSA [6]. While FemX was shown to be essential [7], femAB null mutants were postulated to require a secondary, yet uncharacterized compensatory or suppressor mutation(s) chr* to stabilize the cell [6]. The phenotype of a femAB null mutant thus reflects not only the consequences of the inactivation of the femAB operon, but additionally the effects due to the postulated compensatory mutation(s). These compensatory events or adaptations are of potential interest, as they may tell us about the interrelationship between cell wall synthesis and other cellular mechanisms. By re-introducing the femAB wild type allele in cis, the compensatory effects were separated from those due to the femAB inactivation. This allowed us to study the consequences of the adaptation events in the presence of a restored pentaglycine interpeptide synthesis machinery.
Results and discussion
Phenotypic characterization of the femAB+ backcross
The femAB null mutant AS145 derived from the MRSA BB270 produces only a monoglycine peptidoglycan interpeptide and shows a poorly crosslinked peptidoglycan, aberrant septum formation, methicillin hypersusceptibility, and a reduced growth rate [2]. Back-transduction of the wild type femAB allele in cis by selecting for the upstream, co-transducible, silent insertion Ω2000chr:: Tn551, yielding the backcross strain BB1305, restored methicillin resistance, but did not increase the growth rate [6]. Therefore, survival of AS145 was suggested to require a postulated compensatory mutation termed chr*, which was retained in BB1305. The MRSA strain BB903, which was obtained by transduction of Ω2000chr:: Tn551 into BB270, represents a wild type control strain isogenic to BB1305 except for the postulated chr* mutation (Table 1).
Compared to the highly enlarged cells of AS145, cells of strain BB1305, which were again able to produce a pentaglycine interpeptide, regained the same size as those of the wild type strain BB903 (Figure 1A), suggesting a regular cell separation. The muropeptide pattern of AS145 showed a highly increased amount of uncrosslinked monomeric muropeptides at the cost of the oligomeric peaks as described earlier [2]. The wild type muropeptide profile was then re-established in BB1305 as the characteristic peaks of the dimeric, trimeric, and oligomeric muropeptide fractions were indistinguishable from those of BB903 (Figure 1B). However, calculation of the percentage of free reducing termini in the peptidoglycan revealed on average slightly longer glycan chains in AS145 and BB1305 than in BB903 (Figure 2) as confirmed by two-sided t- test, suggesting that AS145 may have compensated for the poorly crosslinked cell wall by generating longer sugar chains.
In addition to the reduced growth rate, which may be a further strategy to cope with the cell wall defects caused by the femAB deletion, we found that AS145 and BB1305 also shared temperature sensitivity (Figure 3). The autolytic banding patterns and spontaneous and Triton X-100-induced autolysis, at both 37 and 42°C, were virtually identical in the slowly growing femAB+ backcross BB1305 and the wild type BB903 (data not shown), suggesting that there was no correlation between the autolytic behaviour of BB1305 and the reduced growth rates observed. Although the overall autolysis did not differ, subtle modulation in autolytic activities may count for the slightly increased glycan chain length.
The strains used in this study all carry a functional mecA gene and thus are MRSA. A characteristic feature of MRSA strains is the heterogeneous expression of resistance to methicillin and other penicillinase-stable β-lactams such as oxacillin, whereby the majority of cells have only a low resistance level. Upon exposure to inhibitory concentrations of β-lactams, a subpopulation with high resistance is selected. Once formed, high resistance is maintained in absence of selective pressure resulting in MRSA with homogeneous oxacillin resistance. Interestingly, detailed analyses showed that the oxacillin resistance of the femAB+ backcross BB1305 had become higher than that of the parental strain BB270 and of BB903, as shown in the population analysis profiles (Figure 4A) and by growth on an oxacillin gradient plate (Figure 4B). Oxacillin resistance was thus overcompensated in BB1305 and resembled homogeneous resistance as if selected by passage on inhibitory concentrations of oxacillin. In contrast, BB1305 remained hypersusceptible to teicoplanin and bacitracin (Figure 4B). The increased susceptibility to teicoplanin, which interestingly did not extend to vancomycin (data not shown), may indicate changes in the cell membrane with which the lipophilic anchor of teicoplanin interacts [8]. It is therefore likely that the bacitracin and teicoplanin hypersusceptibility of BB1305 and AS145 point to changes in the envelope and membrane organisation.
Transcriptome analysis
Given the multiple phenotypic traits that were not complemented by restoring the pentaglycine interpeptide, changes in the genome transcription profile were expected. In a snapshot of the transcriptomes of exponentially growing cells by microarray analysis, 56 genes were reported to be downregulated in the femAB+ backcross strain BB1305 compared to the wild type strain BB903, and 81 genes were reported to be upregulated [see Additional file 1]. The list of differentially expressed genes was determined using the moderated t-statistics [9], followed by the family-wise error rate (FWER)-based p- value adjustment according to Holm [10], in order to guarantee high confidence in the selected genes.
The distribution of functional classes within the down- and the upregulated genes (Table 2) is depicted in pie charts for comparison with their occurrence within the total of genes represented on the chip (Figure 5). Among the downregulated genes in the mutant, categories significantly overrepresented as determined by Fisher's exact test comprised transport/binding proteins and lipoproteins, protein synthesis, metabolism of lipids, nucleotides and nucleic acids. Taking into account the decreased growth rate of BB1305, this finding may in part reflect the differences in growth between the two strains tested, particularly with regard to protein synthesis. In contrast, the categories that were overrepresented among the upregulated genes, i.e. metabolism of amino acids and carbohydrates, pathogenic factors, and phage-related functions, may point to changes in metabolism selected by an overall stress response to the original femAB deletion.
Metabolic differences
To uncover metabolic differences between the two strains, we made use of recent systems biology advances: In contrast to an otherwise isolated analysis of single genes, we computationally linked the transcriptional data with a recently developed metabolic network model for S. aureus [11] (see Methods). This procedure allowed us to consider the transcriptional differences between the two strains in a metabolic context. The mapping of transcriptional data onto a metabolic network, which underlies the employed computational algorithm, allows to identify spots (so-called reporter metabolites) around which significant regulation occurs, and thus assists in carving out metabolism-related insight from the microarray data. The top scoring reporter metabolites with p-values smaller than 0.05 are listed in Table 3 and an overview of pathways in which many of these reporter metabolites occur is given in Figure 6.
The arginine-deiminase pathway was found to be upregulated in BB1305. This pathway imports extracellular arginine driven by the simultaneous excretion of ornithine via the arginine-ornithine antiporter ArcD (SA2426). Arginine is then converted by the arginine-deiminase (ArcA) to citrulline, which is further metabolized by the ornithine transcarbamoylase (ArcB) to ornithine and carbamoyl phosphate. The carbamate kinase (ArcC) finally breaks down the latter into ammonia and carbon dioxide yielding one ATP. This pathway is perceived to act as an ATP source under anaerobic conditions and in small colony variants (SCV) lacking a functional respiratory chain [12, 13], and it is also thought to be an important player in pH homeostasis as it was also found to be expressed in biofilms [14–16]. Furthermore, depletion of arginine by the arginine-deiminase pathway, which inhibits nitric oxide production in the host, and thus both the innate and the adaptive immune responses against microbial infections, may increase staphylococcal virulence [17].
Another observation was a reduction in glnA expression in the femAB+ backcross BB1305, as was confirmed by Northern blots of the glnRA operon (data not shown). The glutamine synthetase (GS) GlnA produces L-glutamine from L-glutamate and ammonia using one ATP to drive the reaction. Glutamine plays a central role in nitrogen metabolism and functions as an amino group donor in many biosynthetic pathways, leading to the synthesis of histidine, tryptophan, carbamoyl phosphate, glucosamine-6-phosphate, purines, and pyrimidines. A mutation in glnR, which has a polar effect on glnA, results in a decreased GS activity and in a reduction of the amidation of the iD-glutamate of the peptidoglycan stem peptide thereby reducing methicillin resistance [18]. glnA downregulation in BB1305 may reflect an overall reduced requirement for nitrogen due to slowed down growth.
Interestingly, another link to nitrogen metabolism was found in the increased amounts of ureB (urease beta subunit) and ureF (urease accessory protein UreF) transcripts displayed by strain BB1305, which was consistent with the derepression of urease production observed in AS145 and BB1305 in urea-containing medium (Figure 7). On the one hand the urease reaction supplies nitrogen and on the other hand it serves the maintenance of the pH value by formation of ammonium. Urease expression is induced during nitrogen-limited growth [19, 20], and upregulation is observed in glnA mutants [20], growth in biofilms [14, 15], and under heat shock conditions [21].
A downregulation of numerous members of the pyrimidine operon comprising pyrAB, pyrB, pyrC, and pyrE as well as of the regulator pyrR was detected in BB1305. The products of the pyr operon are involved in the de novo synthesis of pyrimidine nucleotides from bicarbonate and from intermediates of the central carbon metabolism or via salvage of preformed pyrimidine bases and nucleotides present in the medium. Transcription of the pyr operon was verified by dot blot analysis because of the large transcript expected, using a pyrP-specific probe (data not shown). A downregulation of the pyr operon was confirmed in early logarithmic growth phase at an optical density at 600 nm (OD600) of 0.4, however, at an OD600 of 1, pyr mRNA levels in BB1305 were the same or even higher than in BB903 (data not shown). In Bacillus subtilis, PyrR controls the expression of the pyr operon by binding to specific sequences of the pyr mRNA thereby leading to attenuation of transcription [22, 23] in response to exogenous uracil and to intracellular UMP/phosphoribosyl pyrophosphate pools [23, 24]. Richardson et al. noted that the pyr operon is repressed in response to nitrosative stress in S. aureus [25]. The upregulation of the arginine-deiminase pathway and the urease reaction as well as the downregulation of the glutamine synthesis may point to a potential action of nitrogen regulators on the pyr operon. Control of pyrR may be exerted by GlnR and TnrA [26–28], since a GlnR/TnrA consensus sequence [27, 29–31] with two mismatches was identified 56 to 38 bp upstream of the coding region of pyrR in the public staphylococcal genomes. While according to the microarray data a reduced transcription of pyrR was expected, signals obtained in Northern blots using a pyrR-specific probe were stronger in BB1305 than in BB903 (data not shown). These were the only discrepancies between microarray data and Northern blots found in the open reading frames tested, leaving the regulation of the pyrimidine operon and the link to the regulation of nitrogen-related functions open.
Cell wall
Although the femAB+ backcross strain BB1305 produced on average slightly longer glycan chains, the transcription of pbpB, coding for the bifunctional PBP2 with transglycosylase activity [32], was not detected to be upregulated, as could have been expected, but downregulated. Furthermore, expression of the soluble glycosyltransferase genes, sgtA and sgtB [33, 34] and of genes coding for glucosaminidases, which may contribute to an increased glycan chain length, could not be detected to be altered. These findings do not rule out a posttranscriptional control of autolytic activities by proteases [35, 36], since three genes encoding proteases (i.e. the cysteine protease SspB, the zinc metalloproteinase aureolysin Aur, and the serine protease-like SplB) were significantly upregulated. In addition, the decreased expression of dltA, dltB, and dltD in BB1305 could also contribute to a lower autolytic activity due to a reduced D-alanine esterification of the teichoic acids [37].
Membrane and transporters
One of the major components of the membrane, lysylphosphatidylglycerol, is a product of the lysylphosphatidylglycerol synthase FmtC (synonym: MprF), which adds a positively charged lysyl residue to phosphatidylglycerol [38, 39]. The fmtC/mprF gene, which belongs to the so-called fem and aux genes, and the inactivation of which reduces methicillin and bacitracin resistance [40, 41], was found to be downregulated in BB1305. Reduced fmtC transcription may on the one hand mirror the reduced growth rate and could on the other hand, by its influence on the membrane charge, also be one of the causes for bacitracin and teicoplanin hypersusceptibility.
One fifth of the genes found differentially regulated in the femAB+ backcross BB1305 code for membrane-associated proteins, mainly transporters and permeases, with the majority showing a reduced transcription level. Interestingly, opuCC, which encodes the substrate-binding protein of a glycine betaine/carnitine/choline ABC transporter, was upregulated as could be confirmed by Northern hybridization showing a stronger transcription of the whole opuC operon in BB1305 than in BB903 (data not shown). The uptake of compatible solutes such as glycine betaine, choline and proline is important in osmotic stress response [42, 43], and the upregulation of opuC may indicate an attempt of the femAB deletion mutant to balance osmotic pressure due to the weakened cell wall. In contrast, opuD and its homologue, sa1987, members of the betaine/carnitine/choline transporter (BCCT) family, were downregulated in BB1305. This latter family of transporters, however, may respond to other kinds of osmotic stress than the opuC operon.
Besides quaternary amines or amino acids, solutes such as polyols (e.g. glycerol, arabitol) and sugars (e.g. sucrose, trehalose) may play a role in osmoprotection [44]. Indeed, genes encoding transporters specific for these classes of compounds were also found to be upregulated in BB1305: namely the glycerol uptake facilitator (glpF), the sucrose-specific IIBC component of the phosphotransferase system (PTS) (scrA), and a hypothetical protein similar to ScrA (sa0186). Other genes encoding sugar transporters were also induced in BB1305, i.e. sa0208/sa0209 (permease homologue of a maltose/maltodextrin ABC transporter), sa0260 (hypothetical protein similar to the ribose transporter RbsU), and sa0318/sa0320 (hypothetical protein similar to the pentitol-specific PTS transporter SgaT/SgaA). Considering the observed upregulation of glpF, it is noteworthy that glpD (aerobic glycerol-3-phosphate dehydrogenase), glpQ (glycerophosphoryldiester phosphodiesterase), and sa0220 (hypothetical protein similar to GlpQ) also appeared to be upregulated in BB1305. These may support osmoprotection as GlpQ catalyzes the conversion of sn-glycero-3-phosphocholine to glycerol-3-phosphate and choline, the latter of which is oxidized to glycine betaine, which is not metabolized further in osmotically stressed S. aureus [45].
Stress response and virulence factors
Given the temperature sensitivity of BB1305, a connection to the heat shock regulon was conceivable. In fact, the gene encoding the chaperone DnaK was downregulated according to the microarray data. DnaK belongs to the HrcA and CtsR controlled heat shock regulon in S. aureus [46]. A dnaK-specific probe, revealed a 3.5 kb-transcript in Northern blot analysis, most probably covering the hrcA operon, and confirmed reduced transcription levels in BB1305 at 37°C (data not shown).
Unfavourable environmental conditions are known to induce lysogenic phages, and the upregulation of phage-related genes in BB1305 is most likely to be regarded in the context of a stress response which occurred in the femAB deletion mutant AS145. Various stress conditions have also been described to trigger the expression of virulence factors [21]. In BB1305, the transcriptional changes observed included the upregulation of a whole series of virulence genes, such as those coding for lipase (lip), urease (ure),α-hemolysin precursor (sa1007), truncated β-hemolysin (sa1752 and sa1811), serine proteases (spl), cysteine protease (sspB) and aureolysin (aur). Since the expression of virulence factors depends on a complex regulatory network, this finding prompted us to analyze the transcription profiles of the major global regulators including sarA (staphylococcal accessory regulator), sae (S. aureus exoprotein expression) and the agr (accessory gene regulator) operon by Northern blot during growth. In accordance with the expression pattern of two representative virulence factors, namely the α-hemolysin precursor (sa1007) and the serine proteases (splABCDEF), the regulators and especially RNAIII and saeRS peaked at a lower OD600 in the femAB+ backcross BB1305 than in BB903. At the transition to stationary phase, at an OD600 of 4, they had already become clearly weaker in the mutant than in the wild type (Figure 8) revealing a remarkably altered timing in the transcription of the main global regulators in BB1305.
This is the first thorough characterization of compensatory effects triggered by a shortened pentaglycine interpeptide, the low ability of PBP to crosslink this altered peptidoglycan, and selection for survival. The poorly crosslinked cell wall may be not strong enough to withstand the cells' high internal turgor. This imbalance must have been sensed by the cells, which found a way to counteract osmotic stress, though at the cost of a decreased growth rate and temperature sensitivity. The rearrangements required also involved changes in the expression of metabolic pathways, especially of the arginine-deiminase pathway and the nitrogen metabolism, and seem to be maintained in a stable manner, since they persisted after restoration of the pentaglycine interpeptide. This demonstrates the vast extent of the compensatory adaptations. Such compensatory adaptations following mutagenesis may happen much more frequently than anticipated, and may be the cause of the often observed experimental inability to fully complement mutations with the original wild type alleles.
Cell wall-deficient forms (L-forms) of S. aureus are able to survive without an intact murein sacculus, and to internalize and persist in macrophages [47]. Adaptive responses to L-forms of S. aureus have recently been described by Fuller et al. [48], who selected cell wall-deficient mutants with subinhibitory concentrations of penicillin in the presence of elevated osmolality. Similar to what we observed, namely that the reconstituted strain BB1305 displayed a higher, more homogeneous oxacillin resistance than the wild type, recovery of the cell wall by the L-forms resulted in a stably inherited penicillin resistance that was independent of a β-lactamase or mecA. Apparently, the expected negative effect of reduced fmtC or glnA expression on oxacillin resistance was compensated in BB1305. A phenomenon, that was also observed with other fem, aux or fmt MRSA mutants which still harboured their original mutations but regained resistance by compensatory events when grown in the presence of β-lactams [18, 49].
The temperature sensitivity and the increased susceptibility to bacitracin and teicoplanin are indications for permanent alterations in the membrane. Membrane defects may also be the cause for the premature upregulation of global regulators which in turn most probably triggered the enhanced expression of virulence factors [50, 51].
It is likely that the adaptations represent just one of many ways that S. aureus could respond to femAB inactivation. Some of the findings may be secondary effects caused by slow growth and changes within the cell, not contributing to survival, similar to the upregulation of the purine operon in vancomycin intermediate resistant S. aureus [52], that did not contribute to increased glycopeptide resistance [53].
At this stage, we cannot confirm that the numerous adaptive events that occurred in the femAB deletion mutant and that are reflected in the femAB+ cis-complemented strain were indeed due to mutation(s). The phenotypic adaptations revealed here, such as temperature sensitivity, slowed down growth, but no changes in autolytic activities, were strikingly similar to the phenotype caused by mutations in femA after selection for lysostaphin resistant clones [54], which might be evidence for a common survival strategy.
S. aureus has shown here a remarkable ability to compensate and survive a severe condition, such as femAB inactivation, which prevents peptidoglycan crosslinking. Implementation of potential FemAB inhibitors may therefore entail selection of resistant subpopulations having unwanted characteristics, making a combined treatment with other antibiotics highly advisable.
Bacterial strains and growth conditions
The strains used in this study are listed in Table 1. Bacteria were cultivated either on sheep blood agar or in Luria Bertani (LB) broth (Becton Dickinson, Sparks, MD) at 37°C, unless stated otherwise. The ratio between broth and culture flask volume was 1:5 and incubation was carried out with shaking at 180 rpm.
Scanning electron microscopy (SEM)
Strains grown in brain heart infusion (BHI) broth at 30°C for 3 h were used to inoculate 1 ml BHI broth in 24-well plates containing polyethylene terephthalate (Thermanox) disks (Life Technologies, Basel, Switzerland) to an OD600 of 0.05. The cells were incubated in stationary culture at 30°C for 2 h. Fixation and SEM were carried out as described previously [55].
Peptidoglycan analysis
Insoluble peptidoglycan was purified from cultures grown to mid-log phase in BHI broth using a standard procedure [56, 57]. After removal of teichoic acids by hydrofluoric acid, the relative glycan chain lengths were determined in the peptidoglycan preparations as described elsewhere [58] and their muropeptide patterns were compared following digestion with muramidase [56].
Antibiotic gradient plates
Qualitative differences in resistance levels were evaluated by swabbing 0.5 McFarland-standard cell suspensions, prepared from freshly grown overnight cultures, along an antibiotic gradient on rectangular LB agar plates. Gradient plates were incubated at 35°C for 24 to 48 h.
Population analysis profile
Overnight cultures were diluted in 0.85% NaCl and aliquots of 0.1 ml were spread onto LB agar plates containing various oxacillin concentrations. Colony forming units (CFUs) were determined after 48 h.
Molecular biological methods
General molecular biology techniques were performed as described by Sambrook et al. [59] and Ausubel et al. [60].
Transcriptional profiling
Overnight cultures were diluted 100-fold in LB broth and cells were grown to an OD600 of 0.8–1.0. The cultures were stabilized by incubation with 2 volumes of RNAprotect Bacteria Reagent (QIAGEN, Hilden, Germany) for 5 min at room temperature. Subsequently, cells were harvested by centrifugation, lysed in the presence of 400 μg/ml lysostaphin (Sigma-Aldrich, Taufkirchen, Germany) and total RNA was isolated using the RNeasy Midi Kit (QIAGEN) following the manufacturers' instructions.
Three independent RNA preparations of each strain were reverse transcribed twice, using either cyanine-3' (Cy3) or cyanine-5' (Cy5) as a label. Briefly, 10 μg of total RNA were transcribed into cDNA using Superscript II reverse transcriptase (Invitrogen, Karlsruhe, Germany). The transcription reaction was performed in the presence of 0.1 mM Cy3- or Cy5-labelled dCTP (Perkin Elmer Life Science, Mechelen, Belgium) in addition to 0.2 mM dCTP, 0.5 mM dATP, dGTP and TTP, 75 μg/ml random hexamer primer (Amersham, Bioscience, Freiburg, Germany) and 4U/μl RNase-Out (Invitrogen). RNA was degraded by alkaline hydrolysis at 65°C and cDNA was purified using the MinElute PCR Purification Kit (QIAGEN).
Differentially labelled cDNAs of both strains were competitively hybridized with a custom PCR product microarray (Scienion, Berlin, Germany) resulting in a total of six chips. The microarray contained 2332 open reading frames (ORFs) of the S.aureus N315 genome, each represented by adjacent duplicate spots. Hybridization was performed at 42°C for 72 h according to the manufacturer's instructions. The hybridized microarrays were read out with a GenePix 4000B scanner (Axon Instruments/Distribution by Biozyme, Oldendorf, Germany). Image analysis and acquisition of relative data were conducted using GenePixPro 4.1 software (Axon Instruments).
Microarray data analysis
First, the intensity data arising from the six two-colour spotted microarrays were calibrated and normalized in order to remove systematic technical variation (e.g. different labelling efficiencies and scanning properties of the Cy3 and Cy5 dyes) and to ensure that observed differences in intensities indeed reflect biological signal. Two-channel normalization was performed to adjust the centre and spread of the distribution of intensity log-ratios [61] using the default method of the "marray" package [62] in Bioconductor version 1.8 [63]. Adaptive location normalization within print-tip groups using robust local regression [64] allows the capture of non-linear dependencies of the intensity log-ratio on overall intensity, while ensuring that the computed normalization values are not driven by a small number of differentially expressed genes with extreme log-ratios. Due to scale differences between the arrays we also conducted global scale normalization across arrays.
For identification of differentially expressed genes between the femAB+ backcross BB1305 and the wild type BB903, the linear modelling features of the "limma" R package version 2.9.1 were used [65]. In the present experiment, three BB1305 RNA preparations were to be compared with three BB903 RNA preparations using six arrays, i.e. each RNA appeared on two different arrays. Note that technical replicates are not independent: in fact they are likely to be positively correlated. Since the experimental design did not arrange the arrays in groups of biological replicates, we fitted a model with a coefficient for each RNA preparation. The duplicate spots in adjacent position were taken into account by estimating a common value for the intra-duplicate correlation [66] that was used when fitting a linear model for each gene. Finally, we extracted the contrast referring to the average expression differences between the two investigated S. aureus strains and computed moderated t-statistics using empirical Bayes methods. These borrow information across genes and thus stabilize the analysis even for a small number of arrays [9]. The reported list of potentially interesting genes was determined by adjusting the p-values for multiple testing. Here we have chosen the FWER-based p-value adjustment according to Holm [10], where the multiple significance level α was set to 0.05.
Reporter metabolite analysis
The microarray data were further analyzed by a recently developed algorithm that uses the topology of an organism's metabolic network to uncover underlying metabolism-related transcriptional regulation [67]. This algorithm first converts a genome-scale metabolic network of S. aureus N315 [11] into a bipartite metabolic graph. In this graph, each metabolite node is then scored based on the normalized transcriptional response of its neighbouring enzymes. Using the genes' p-values as inputs to score the enzyme nodes, the algorithm identifies so-called reporter metabolites, designating metabolites around which the most significant transcriptional changes occur.
Northern blots
The transcription of a selection of genes was verified by Northern hybridization and primers used for probe amplification are listed in Table 4. Overnight cultures were diluted 100-fold in LB broth and incubated for 2 h. The pre-cultures were then diluted in LB broth to an OD600 of 0.05 and grown until they reached the desired OD600. Total RNA was extracted according to the method of Cheung et al. [68]. For Northern hybridization, 8 μg of total RNA per sample were loaded on a 1.5% agarose gel containing 20 mM guanidine thiocyanate in 1xTris-Borate-EDTA running buffer [69]. Blotting of the electrophoretically separated RNA and detection of transcripts were carried out as described earlier [70].
Urease assay
McFarland 0.5-standard cell suspensions were diluted 100-fold in urea medium [71] and were incubated in 96-well plates at 37°C for 24 hours.
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This study was supported by LSHM-CT-2003-503335 (SBF03.0098) and Swiss National Science Foundation grant 31-105390/1 to B.B.-B., a grant of the Federal Ministry of Education and Research of Germany (Pathogenomics, PTJ-BIO/03U213B, 601 I 1-4/1 - V II ZV -03, V I PG 1) to G.B., Swiss National Science Foundation grant 3200B0-103793 to P.A.M., and financial support from DSM Nutritional Products to J.S.
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Authors' contributions
JH carried out phenotypic characterizations and Northern blots, experimentally validated the microarray data, contributed to the interpretation of the results, and drafted the manuscript. AJ carried out the microarrays. OK performed the reporter metabolite analysis. JS performed the statistical analyses. PAM conducted the peptidoglycan analyses. LGH carried out the scanning electron microscopy. GB participated in the design of the microarray experiments and their interpretation. MH supervised the reporter metabolite analysis and interpreted its results. BBB conceived, designed, and coordinated the study, and participated in writing of the manuscript. All authors read and approved the final manuscript.
Electronic supplementary material
Additional file 1: Genes found differentially expressed in the femAB+ backcross BB1305 compared to the wild type BB903. The selection of regulated genes is based on statistical significance of moderated t-scores and thus also includes genes with a log2(fold change) < |1|. The genes are clustered according to their cellular main role as in the S. aureus N315 genome annotation on the DOGAN website [73]. (PDF 82 KB)
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Hübscher, J., Jansen, A., Kotte, O. et al. Living with an imperfect cell wall: compensation of femAB inactivation in Staphylococcus aureus. BMC Genomics 8, 307 (2007). https://doi.org/10.1186/1471-2164-8-307
DOI: https://doi.org/10.1186/1471-2164-8-307


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Gonadorelin (Intravenous, Injection)
Generic name: gonadorelin [ goe-nad-oh-REL-in ]
Drug class: Gonadotropin releasing hormones
Medically reviewed by Drugs.com. Last updated on Mar 26, 2023.
Uses for gonadorelin
Gonadorelin is a medicine that is the same as gonadotropin-releasing hormone (GnRH) that is naturally released from the hypothalamus gland. GnRH causes the pituitary gland to release other hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]). LH and FSH control development in children and fertility in adults.
Gonadorelin is used to test how well the hypothalamus and the pituitary glands are working. It is also used to cause ovulation (release of an egg from the ovary) in women who do not have regular ovulation and menstrual periods because the hypothalamus gland does not release enough GnRH.
Gonadorelin may also be used for other conditions as determined by your doctor.
Before using gonadorelin
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
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Breast Feeding
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with Medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Bepridil
- Cisapride
- Dronedarone
- Levoketoconazole
- Mesoridazine
- Pimozide
- Piperaquine
- Saquinavir
- Sparfloxacin
- Terfenadine
- Thioridazine
- Ziprasidone
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Adagrasib
- Alfuzosin
- Amiodarone
- Amisulpride
- Amitriptyline
- Anagrelide
- Aripiprazole
- Aripiprazole Lauroxil
- Arsenic Trioxide
- Asenapine
- Astemizole
- Atazanavir
- Azithromycin
- Bedaquiline
- Buprenorphine
- Ceritinib
- Chloroquine
- Chlorpromazine
- Ciprofloxacin
- Citalopram
- Clarithromycin
- Clofazimine
- Clomipramine
- Clothiapine
- Clozapine
- Crizotinib
- Cyclobenzaprine
- Dabrafenib
- Dasatinib
- Delamanid
- Desipramine
- Deutetrabenazine
- Dexmedetomidine
- Disopyramide
- Dofetilide
- Dolasetron
- Domperidone
- Donepezil
- Doxepin
- Droperidol
- Ebastine
- Efavirenz
- Encorafenib
- Entrectinib
- Eribulin
- Erythromycin
- Escitalopram
- Famotidine
- Felbamate
- Fexinidazole
- Fingolimod
- Flecainide
- Fluconazole
- Fluoxetine
- Formoterol
- Foscarnet
- Fosphenytoin
- Fostemsavir
- Galantamine
- Gatifloxacin
- Gemifloxacin
- Gepirone
- Glasdegib
- Granisetron
- Halofantrine
- Haloperidol
- Hydroquinidine
- Hydroxychloroquine
- Hydroxyzine
- Ibutilide
- Iloperidone
- Imipramine
- Inotuzumab Ozogamicin
- Itraconazole
- Ivabradine
- Ivosidenib
- Ketoconazole
- Lapatinib
- Lefamulin
- Lenvatinib
- Leuprolide
- Levofloxacin
- Lofexidine
- Lumefantrine
- Macimorelin
- Mefloquine
- Methadone
- Metronidazole
- Mifepristone
- Mirtazapine
- Mizolastine
- Mobocertinib
- Moxifloxacin
- Nelfinavir
- Nilotinib
- Norfloxacin
- Octreotide
- Ofloxacin
- Olanzapine
- Ondansetron
- Osilodrostat
- Osimertinib
- Oxaliplatin
- Ozanimod
- Pacritinib
- Paliperidone
- Panobinostat
- Paroxetine
- Pasireotide
- Pazopanib
- Pentamidine
- Perphenazine
- Phenobarbital
- Pimavanserin
- Pipamperone
- Pitolisant
- Ponesimod
- Posaconazole
- Primidone
- Probucol
- Procainamide
- Prochlorperazine
- Promethazine
- Propafenone
- Protriptyline
- Quetiapine
- Quinidine
- Quinine
- Quizartinib
- Ranolazine
- Relugolix
- Ribociclib
- Rilpivirine
- Risperidone
- Ritonavir
- Selpercatinib
- Sertindole
- Sertraline
- Sevoflurane
- Siponimod
- Sodium Phosphate
- Sodium Phosphate, Dibasic
- Sodium Phosphate, Monobasic
- Solifenacin
- Sorafenib
- Sotalol
- Sulpiride
- Sunitinib
- Tacrolimus
- Tamoxifen
- Telaprevir
- Telavancin
- Telithromycin
- Tetrabenazine
- Tolterodine
- Toremifene
- Trazodone
- Triclabendazole
- Trimipramine
- Vandetanib
- Vardenafil
- Vemurafenib
- Venlafaxine
- Vilanterol
- Vinflunine
- Voclosporin
- Voriconazole
- Vorinostat
- Zuclopenthixol
Interactions with Food/Tobacco/Alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
Other Medical Problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Gonadotropin-releasing hormone adenoma—Although this condition is rare, use of gonadorelin when this condition exists may cause problems in the pituitary gland and could result in sudden blindness
- Any condition that may be made worse by estrogens, progestins, or androgens, such as a hormone-dependent tumor—The increase of estrogens and progestins in women or androgens in men that can result from use of multiple doses of gonadorelin may make a tumor worse if the tumor depends on estrogens, progestins, or androgens for growth
Proper use of gonadorelin
If you are having a test done with gonadorelin, one or more samples of your blood will be taken. Then gonadorelin is given by an intravenous (into a vein) or a subcutaneous (under the skin) injection. At regular times after the medicine is given, more blood samples will be taken. Then the results of the test will be studied.
Some medicines given by injection or by injection pump may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, make sure you clearly understand and carefully follow your doctor's instructions.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For injection dosage form (for Lutrepulse pump):
- For treating amenorrhea or infertility in women caused by pituitary or hypothalamus problems:
- Adults—5 microgram (mcg) injected by the pump into a vein or under the skin slowly over 1 minute, every ninety minutes for twenty-one days. As determined by doctor, dose may be changed slowly, decreased to 1 mcg or increased to 20 mcg if needed.
- Children up to 18 years of age—Use and dose must be determined by the doctor.
- For treating amenorrhea or infertility in women caused by pituitary or hypothalamus problems:
- For injection dosage form (single-dose injection):
- For testing the hypothalamus and pituitary glands:
- Adults—0.1 milligram (mg) injected once as a single dose under the skin or into a vein.
- Children 12 years of age and older—2 micrograms (mcg) per kilogram (kg) (0.9 mcg per pound) of body weight, not to exceed a single dose of 100 mcg, injected once under the skin or into vein.
- Children up to 12 years of age—Use and dose must be determined by doctor.
- For testing the hypothalamus and pituitary glands:
Precautions while using gonadorelin
For Lutrepulse pump—It is very important that your doctor check your progress at regular visits. This will allow the doctor to see if the medicine is working properly and to decide if you should continue to use it.
If you are using gonadorelin to help you become pregnant, closely follow your doctor's advice on the best times to have sexual intercourse. Your doctor can help you decide when having sexual intercourse will not result in a pregnancy with twins or triplets.
Tell your doctor when you suspect your are pregnant.
Side Effects of gonadorelin
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
With repeated doses
- Difficulty in breathing
- flushing (continuing)
- rapid heartbeat
Check with your doctor as soon as possible if any of the following side effects occur:
With repeated doses
- Hardening of skin at place of injection
- hives
With single or repeated doses
- Itching, pain, redness or swelling of skin at place of injection
- skin rash (at place of injection or over entire body)
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Less common
With single dose
- Abdominal or stomach discomfort
- flushing (lasting only a short time)
- headaches
- lightheadedness
- nausea
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
More about gonadorelin
- Check interactions
- Compare alternatives
- Reviews (1)
- Latest FDA alerts (1)
- Side effects
- Dosage information
- Drug class: gonadotropin releasing hormones
Patient resources
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Related treatment guides
Further information
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With buns for long hair you can unleash your imagination. Style your locks tousled and disheveled or smooth and sleek. Try waves, curls and poker straight strands in loose knots and edgy buns. Celebrities are ready to share their most flattering and stylish bun updos with you!
Bun Hairstyles for Long Hair
#1: Carefree Beach Curls Bun
Anna Lynne McCord rocks this stunning messy bun that is perfect for naturally curly hair. The style looks cool with its maximum volume, but you still should pin random locks away from your face for a beautiful framing effect. Stray wisps are blown back and held with hairspray for a fun and carefree look.
Helga Esteb / Shutterstock.com


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Photos Credit: Vision Events Photography
As regular readers of this Blog already know the British Columbia wines have improved by leaps and bounds in the last few years. Helped somewhat by global warming, winemaking experience and other vineyard factors there are current releases that are outstanding. The recognition of some unique key factors has contributed to this excellence and the distinct terroir that is evolving: good levels of natural acidity and tannins for the intense pure fruit flavours (including complex sage, tree fruits, herbs, earth) from long sunlight hours with dramatic swings between warm days and cool nights. Though far north at 49-50 degrees latitude many vineyards enjoy the benefits of this unusual hot dry desert short growing season which is so conducive to sustainable farming.
Therefore the timing was appropriate to test this theory on the visit this August for a week to the Okanagan Valley & Vancouver by world recognized wine expert Steven Spurrier consulting editor of Decanter and chair of their World Wine Awards with a "Judgment of BC" tasting. It also celebrated the 25th anniversary of BC VQA (Vintner's Quality Alliance) a guarantee that the wine is made from 100% BC grown grapes. They now are promoting this with "BC VQA. Or You Could Call it BC DNA". Back in 1976 Steven organized the historic "Judgment of Paris" comparing California wines against French. Seventeen acknowledged wine "pros" who know BC wines including your scribe accepted the invitation to rank blind 12 chardonnay and 12 syrah in separate flights each containing 6 from BC and 6 International benchmarks. Wine educator DJ Kearney (@djwines) the curator of this event together with Wines of British Columbia (www.winebc.com; @WineBCdotcom) did an outstanding orchestration of this tasting using the best wine glasses, serving at perfect wine temperatures, white table mats, natural light, adequate time to study the wine in the glass etc. Well done.
CHARDONNAY: A controversial choice because nearly every wine region is making international chardonnay but some regions are delivering a very special recognizable terroir. BC has some high quality examples but not enough distinct unique style to differentiate it from most other chardonnay around the world. Would prefer showing the success of Riesling (plantings from 1978), Chenin Blanc (plantings from 1968), Rhone blends (Viognier, Rousanne, Marsanne) or even the most planted variety Pinot Gris – which sometimes can be a little boring. The results with no BC chardonnay in the top 5 was not a surprise to me.
SYRAH: A very good choice because certainly syrah is impressive from BC. Magically combines both characteristics of rich ripe intense fruit from warmer climate regions together with fresher, black pepper, gamey, floral, and the more balanced style of cooler regions. Not unexpected to me with the results ranking first, fourth & fifth and showing clearly that BC Syrah is world class among its peers. Cabernet Franc, Pinot Noir, Gamay Noir, or even the most planted variety Merlot would be good choices for hopefully the second edition of this event. Steven tried many pinot noir wines during his Okanagan Valley visit and was impressed with "the elegance and the true Burgundian style of this variety". Yes Foxtrot Vineyards 2012 and others are really singing. He also noted " For me wine is the three "P's": the Place, the People, and the Product. British Columbia ticks all these boxes with exuberance, elegance and conviction". BC Bottle Shock? Perhaps. For some yes. For me no. The results of both blind tastings are as follows:
- Soumah Single Vineyard 2013 Yarra Valley Victoria $27 – 12.7 degrees alcohol Bottled November 2013 Poured 4th
- Kumeu River Hunting Hill 2012 Auckland New Zealand $35 – 13.5 Poured 12th
- Hamilton Russell 2014 Hemel-en-Aarde South Africa $40 – 13. Poured 10th
- Jean-Marc Brocard Chablis 1er Cru Montmains 2012 France $45 – 13. Poured 1st
- Bouchard Pere Meursault 1er Cru Genevrieres 2011 France $86 – 13.5 Poured 5th
- Blue Mountain Reserve 2012 Okanagan Valley BC $30 – 13.5 Poured 2nd
- Tantalus 2012 $24 – 14. Poured 6th
- Robert Mondavi Reserve 2012 Carneros California $44 – 13.5 Poured 8th
- Mission Hill Perpetua 2012 Okanagan Valley BC $50 Poured 9th
- (Tie for 9th) Quails' Gate Rosemary's Block 2013 Okanagan Valley BC $30 – 13. Poured 11th
- Meyer Family Micro Cuvee 2012 Okanagan Valley BC $65 -13.5 Poured 3rd
- Haywire Canyonview 2013 $25 – 14. Poured 7th
- CC Jentsch 2013 Okanagan Valley BC $30 – 13.8 Also just won Platinum at National Wine Awards 2015 Poured 5th
- Langmeil Orphan Bank 2012 Barossa South Australia $68 – 14.5 Vines 70 years old Poured 4th
- Domaine Vincent Paris Cornas Granit 60 2013 Rhone France $66 – 13. Poured 6th
- Nichol Okanagan Valley BC $40 – 12.8 Poured 1st
- Le Vieux Pin Cuvee Classique 2013 Okanagan Valley BC $50 14.1 Poured 11th
- Ojai 2011 Santa Barbara California $30 Poured 3rd
- Jackson-Triggs Sunrock 2010 Okanagan Valley BC $30 – 13.5 Poured 7th
- Orofino Scout Vineyard 2012 Similkameen Valley BC $29 – 14.7 Poured 12th
- JL Chave Crozes-Hermitage Silene 2012 Rhone France $40 – 13. Poured 2nd
- Tyrrell Vat 9 2011 Hunter Valley New South Wales $49 – 12.9 Poured 10th
- Laughing Stock 2013 Okanagan Valley BC $38 – 14.2 Poured 8th
- K Vintners The Beautiful 2012 Walla Walla Washington $70 – 14.5 Poured 9th
(L-R) Sid Cross, Steven Spurrier, Barb Philip MW, David Scholefield.
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Do safer seizure medication choices during pregnancy result in fewer birth defects?About seizures and epilepsy
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In their study "Declining malformation rates with changed antiepileptic drug prescribing: An observational study," Dr. Tomson and coauthors1 analyzed 14 years of data from pregnant women with epilepsy. Their goal was to find out how seizure medication choices and pregnancy outcomes have changed over time. The data came from an international pregnancy data registry called EURAP.
What is the EURAP registry and how does it work?
A clinical data registry is a database that records medical information about patients over time to gather knowledge about particular medical conditions. EURAP is an international registry that records data about pregnant women who take seizure medications in Europe, Australia, Asia, and South America.2 There is a separate pregnancy registry in the United States and Canada called the North American Antiepileptic Drug Pregnancy Registry.3
The EURAP registry currently includes data from over 25,000 patients in 44 countries since 1999.2 Before there were pregnancy registries for women with epilepsy, little was known about the safety of seizure medications during pregnancy. This is because pregnant women cannot go through drug trials. The main goal of EURAP is to learn about risks associated with taking seizure medications during pregnancy, and to record any birth defects that occur.4 Doctors encourage pregnant women who have been taking seizure medications since conception to enroll in the registry to help us learn about seizure medication safety in pregnancy.
What have we learned from the EURAP registry in previous research?
Multiple studies about seizure medication safety during pregnancy have been published since the EURAP registry began. A recent large study including data from 7,355 pregnancies was published by Dr. Tomson and colleagues4 in 2018. The study included women who were taking 1 of the 8 common seizure medications.
The authors found that the seizure medication associated with the highest rate of birth defects was valproate (10.3% of pregnancies) (table). Other medications with higher rates of birth defects included phenobarbital, phenytoin, and carbamazepine. Medications with lower rates of birth defects included oxcarbazepine, levetiracetam, and lamotrigine. Risks of birth defects for oxcarbazepine, levetiracetam, and lamotrigine were between 2% and 3%, which is similar to the rate of birth defects in women who do not take seizure medications.
What were the main findings of this study?
The goals of the current study were to determine whether doctors have changed their seizure medication choices in pregnant women based on new safety data published previously from the EURAP registry. They also asked whether those medication choices have resulted in a decreased rate of birth defects in babies born to these women.
Study of EURAP data from 2000 to 2013 showed that there was a decline in use of higher risk medications and an increase in lower risk medications levetiracetam and lamotrigine over time. The rate of birth defects decreased over time, from 6.0% in 2000–2005 to 4.4% in 2010–2013. This is a 27% decrease (figure). Birth defect rates for individual medications stayed about the same, although birth defect rates for all medications combined went down. This reflects the shift to use of lower risk medications. The rate of convulsive (generalized tonic-clonic) seizures reported during pregnancy did not change.1
What does this mean for pregnant women with epilepsy?
This study found a change in prescribing patterns. Doctors are prescribing fewer higher risk seizure medications for pregnant women and more lower risk seizure medications. The overall rate of birth defects decreased over time. There was evidence that the reduction in birth defects was related to decreasing use of higher risk medications, particularly valproate. Other reasons such as improving prenatal care did not explain the improvement. The change in medications used during pregnancy did not result in more serious seizures.
These results give doctors and patients more confidence that it is safer to choose levetiracetam and lamotrigine when possible for pregnant women with epilepsy over higher risk seizure medications.
See Page 379
Patient Pages: NPub.org/patient
- © 2019 American Academy of Neurology
- 1.↵
- Tomson T,
- Battino D,
- Bonizzoni E, et al
- 2.↵EURAP. International Registry of Antiepileptic Drugs and Pregnancy [website]. Available at: eurapinternational.org. Accessed May 5, 2019.
- 3.↵The North American Antiepileptic Drug Pregnancy Registry [website]. Available at: aedpregnancyregistry.org/. Accessed May 5, 2019.
- 4.↵
- Tomson T,
- Battino D,
- Bonizzoni E, et al
About seizures and epilepsy
Adapted from Smith DM. Genetic testing: About epilepsy and genetics. Neurology 2019;92:e523–e526; and Karceski S. Pregnancy, antiseizure medications, and seizures: About epilepsy. Neurology 2018;91:e1271–e1274.
What are seizures?
The cells of your brain use chemicals and electrical signals to talk to each other. Most of the time, this electricity is like a room of people talking—there is constant chatter but none of the voices stand out. If a group of cells starts sparking off electricity together in coordination with each other, it is as if they are talking loudly together, making a sound that can be heard above the crowd. The coordinated electrical signals create a sort of electrical storm or surge, which is a seizure. Seizures can look like many different things, depending on how many cells are talking, and where those cells are in the brain.
This is why there are many different types of seizures. Most people have heard of the grand mal type seizure, where a person becomes stiff all over and has shaking movements of the whole body. Other seizures may look similar to this, only involving one half of the body. People may or may not lose consciousness during a seizure. A seizure can be nothing more than a muscle jerk, over in less than a second. It can be a few seconds of staring off. It can vary a great deal from person to person.
What is epilepsy?
People have seizures for different reasons. Some children have seizures when they have a high fever. Some people with diabetes have seizures when their blood sugar gets low. These seizures are provoked, or set off, by something else. It is the fever or the blood sugar that is the problem, not the brain. In epilepsy, there is nothing provoking the seizures. Seizures happen for no reason. In epilepsy, doctors use seizure medications to prevent seizures. In provoked seizures, doctors usually do not use seizure medications.
What causes epilepsy?
There are many different reasons why people can get epilepsy. Sometimes, epilepsy happens after there is an injury to the brain. For example, epilepsy can happen after a concussion, after a stroke, or after a brain infection. Sometimes, doctors can tell the cause of epilepsy by looking at a picture of the brain. However, for many people, no brain injury ever happened, and there is nothing wrong on the picture of their brain. For many of these people, their epilepsy may be genetic, or may be caused by a problem too small to see with a brain scan.
How are seizures treated?
There are many treatments for seizures. Medicines are tried first. If these do not work, a doctor may consider special diets, brain surgery, or devices for the treatment of seizures. The goal is to stop all seizures without causing side effects. In women who are pregnant, or thinking about becoming pregnant, it is especially important to consider safety when choosing medications. There are certain medications that are known to have a higher association with birth defects. Often, in women who are thinking about starting a family, these medications are avoided. When choosing a medication, it is important to have a discussion with your doctor about your life plans: work, exercise, and the desire to start a family. Taking all of these things into consideration, together you will make the best choice of treatments.
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You May Also be Interested in
- Article
- What is the EURAP registry and how does it work?
- What have we learned from the EURAP registry in previous research?
- What were the main findings of this study?
- What does this mean for pregnant women with epilepsy?
- Footnotes
- References
- What are seizures?
- What is epilepsy?
- What causes epilepsy?
- How are seizures treated?
- Figures & Data
- Info & Disclosures
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